ORCID Profile
0000-0001-5449-2838
Current Organisation
Macquarie University
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Research Topics
In Research Link Australia (RLA), "Research Topics" refer to ANZSRC FOR and SEO codes. These topics are either sourced from ANZSRC FOR and SEO codes listed in researchers' related grants or generated by a large language model (LLM) based on their publications.
Top 5 Research Topics
ANZSRC Field of Research (FoR)
Organic Chemistry | Analytical Biochemistry | Biological And Medical Chemistry | Biochemistry and Cell Biology | Organic Chemical Synthesis | Basic Pharmacology | Palaeoclimatology | Physical Organic Chemistry | Natural Products Chemistry | Geochemistry | Cell Neurochemistry | Biotechnology Not Elsewhere Classified | Enzymes | Organic Geochemistry
ANZSRC Socio-Economic Objective (SEO)
Chemical sciences | Biological sciences | Scientific instrumentation | Air quality | Oil and gas | Preventive medicine | Earth sciences |
Related Links
Publications
Characterisation of a novel UV filter in the lens of the thirteen-lined ground squirrel (Ictidomys tridecemlineatus)
Publisher: Elsevier BV
Date: 04-2014
DOI: 10.1016/J.EXER.2014.01.022
Abstract: Structural analysis of a novel UV filter present in the lens of the thirteen-lined ground squirrel has shown that it is related in structure to N-acetyl-3-hydroxykynurenine. This finding is consistent with the fact that the squirrel lenses also contain high levels of this tryptophan metabolite. Analysis of both NMR and mass spectrometric data suggested that the novel UV filter compound forms by condensation of proline with N-acetyl-3-hydroxykynurenine. Its absorption maximum at 340 nm is more than 20 nm lower than that of the kynurenines and it may therefore assist in filtering the more damaging shorter wavelengths of UVA.
Inhibition of indoleamine 2,3 dioxygenase activity by H2O2
Publisher: Elsevier BV
Date: 06-2006
DOI: 10.1016/J.ABB.2006.03.003
Abstract: Indoleamine 2,3-dioxygenase is the first and rate limiting enzyme of the kynurenine pathway of tryptophan metabolism, has potent effects on cell proliferation and mediates antimicrobial, antitumorogenic, and immunosuppressive effects. As a potent cytotoxic effector, the mechanisms of indoleamine 2,3-dioxygenase inhibition deserve greater attention. The work presented here represents the first systematic study exploring the mechanisms by which low levels of hydrogen peroxide (10-100 microM) inhibit indoleamine 2,3-dioxygenase in vitro. Following brief peroxide exposure both enzyme inhibition and structural changes were observed. Loss of catalysis was accompanied by oxidation of several cysteine residues to sulfinic and sulfonic acids, observed by electrospray and MALDI mass spectrometry. Enzyme activity could in part be preserved in the presence of sulfhydryl containing compounds, particularly DTT and methionine. However, these structural alterations did not prevent substrate (l-tryptophan) binding. Some enzyme activity could be recovered in the presence of thioredoxin, indicating that the inhibitory effect of H(2)O(2) is at least partially reversible in vitro. We present evidence that cysteine oxidation represents one mechanism of indoleamine 2,3-dioxygenase inhibition.
Traditional medicine partnerships – fostering two way exchange of knowledge, skills and capacity strengthening
Publisher: International Society for Horticultural Science (ISHS)
Date: 11-2016
Rectal gland exudates and emissions of Bactrocera bryoniae: chemical identification, electrophysiological and pheromonal functions
Publisher: Springer Science and Business Media LLC
Date: 28-11-2020
Natural Product-Inspired Pyranonaphthoquinone Inhibitors of Indoleamine 2,3-Dioxygenase-1 (IDO-1)
Publisher: CSIRO Publishing
Date: 2013
DOI: 10.1071/CH12393
Abstract: A series of pyranonaphthoquinone derivatives possessing structural features present in both natural products annulin B and exiguamine A have been shown to exhibit low micromolar inhibition of indoleamine 2,3-dioxygenase-1 (IDO-1). These inhibitors retain activity against the enzyme in a cellular context with an approximate one-log loss of dose potency against IDO-1 in cells. One particular analogue, triazole 8 shows good inhibition of IDO-1 along with little loss of cell viability at low drug concentrations. These results have extended the naphthoquinone series of novel IDO-1 inhibitors based on lead compounds from nature.
A chromene acid from Calophyllum cordato-oblongum
Publisher: Elsevier BV
Date: 05-1999
Novel Protein Modification by Kynurenine in Human Lenses
Publisher: Elsevier BV
Date: 02-2002
UV Filter Instability: Consequences for the Human Lens
Publisher: Elsevier BV
Date: 08-2002
Abstract: Human lenses appear to become coloured with age primarily due to the covalent binding of UV filter compounds to lens proteins. These crystallin modifications result from the inherent instability of the kynurenine UV filters. Here we investigate this decomposition, the role this may have in the formation of other primate UV filters, and the interaction of the intermediates (alpha,beta-ketoalkenes) with lens components. The UV filters kynurenine, 3-hydroxykynurenine and 3-hydroxykynurenine glucoside were incubated at neutral pH in the presence or absence of NADH or NADPH. The three UV filters underwent spontaneous deamination, such that at pH 7 less than half of the starting materials (kynurenine (42%), 3-hydroxykynurenine glucoside (30%) and 3-hydroxykynurenine (21%)) remained after 7 days. In the presence of NAD(P)H, the double bond of the UV filter-derived deamination compounds, were reduced. Deamination of 3-hydroxykynurenine glucoside, followed by reduction with NAD(P)H, could thus account for the formation of the major lens UV filter 4-(2-amino-3-hydroxyphenyl)-4-oxobutanoic acid glucoside. beta-Benzoylacrylic acid, which possesses the same alpha,beta-ketoalkene sidechain as the deaminated kynurenine UV filters, underwent Michael addition with glutathione, was reduced (hydrogenated) by NAD(P)H, however was unreactive with ascorbate. Surprisingly, at pH 7 the UV filter-derived alpha,beta-ketoalkene intermediates, do not readily undergo intramolecular cyclization. This feature makes the double bond more available for reaction with protein nucleophilic residues and other lens components such as glutathione. On the basis of these data it is likely that glutathione and NAD(P)H, but not ascorbate, protect proteins in the lens from modification by UV filters.
Lenticular Levels of Amino Acids and Free UV Filters Differ Significantly between Normals and Cataract Patients
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 11-2004
DOI: 10.1167/IOVS.04-0178
Abstract: To determine the levels of free UV filters and selected amino acids in cataract lenses compared with normal lenses. Indian cataract lenses (n=39) and normal lenses (n=6) were examined by HPLC to quantify levels of UV filter compounds, the UV filter precursor amino acid tryptophan (Trp), as well as tyrosine (Tyr) and uric acid. The levels of the two major primate UV filters, 3-hydroxykynurenine glucoside (3OHKG) and 4-(2-amino-3-hydroxyphenyl)-4-oxobutanoic acid glucoside (AHBG), in cataract lenses were markedly decreased compared with levels in normal lenses. By contrast, the levels of Trp were greatly increased. Mean Trp concentrations were an order of magnitude higher than in normal lenses, with 86% of dark-colored cataract lens nuclei having Trp concentrations greater than the mean level in the normal lenses. The concentrations of Tyr were also higher in cataract lenses. The levels of Kyn, however, were unchanged, and the uric acid levels were substantially lower. The levels of the free UV filter compounds 3OHKG and AHBG, and also of Trp, Tyr, and uric acid were different in cataract lenses compared to normal lenses. These data suggest that the metabolism of a large proportion of patients with cataract may be substantially different than in persons with normal lenses. Although the mechanism of such metabolic defects are unknown, the authors speculate that an amino acid transporter system may be upregulated in patients with cataract. Because kynurenine levels in cataract were not significantly different from those of normal lenses, there may be a defect in the lenticular UV filter pathway at one, or both, of the steps that convert kynurenine to 3OHKG.
Raspberry Ketone Analogs: Vapour Pressure Measurements and Attractiveness to Queensland Fruit Fly, Bactrocera tryoni (Froggatt) (Diptera: Tephritidae)
Publisher: Public Library of Science (PLoS)
Date: 19-05-2016
Spontaneous Cleavage of Proteins at Serine Residues
Publisher: Springer Science and Business Media LLC
Date: 03-05-2011
Mammalian forebrain ketimine reductase identified as μ‐crystallin; potential regulation by thyroid hormones
Publisher: Wiley
Date: 15-03-2011
DOI: 10.1111/J.1471-4159.2011.07220.X
Abstract: Ketimine reductase (E.C. 1.5.1.25) was purified to apparent homogeneity from lamb forebrain by means of a rapid multi-step chromatography protocol. The purified enzyme was identified by MS/MS (mass spectrometry) as μ-crystallin. The identity was confirmed by heterologously expressing human μ-crystallin in Escherichia coli and subsequent chromatographic purification of the protein. The purified human μ-crystallin was confirmed to have ketimine reductase activity with a maximum specific activity similar to that of native ovine ketimine reductase, and was found to catalyse a sequential reaction. The enzyme substrates are putative neuromodulator/transmitters. The thyroid hormone 3,5,3'-l-triiodothyronine (T3) was found to be a strong reversible competitive inhibitor, and may have a novel role in regulating their concentrations. μ-Crystallin is also involved in intracellular T3 storage and transport. This research is the first to demonstrate an enzyme function for μ-crystallin. This newly demonstrated enzymatic activity identifies a new role for thyroid hormones in regulating mammalian amino acid metabolism, and a possible reciprocal role of enzyme activity regulating bioavailability of intracellular T3.
Electrophysiological Responses of Bactrocera kraussi (Hardy) (Tephritidae) to Rectal Gland Secretions and Headspace Volatiles Emitted by Conspecific Males and Females
Publisher: MDPI AG
Date: 19-08-2021
DOI: 10.3390/MOLECULES26165024
Abstract: Pheromones are biologically important in fruit fly mating systems, and also have potential applications as attractants or mating disrupters for pest management. Bactrocera kraussi (Hardy) (Diptera: Tephritidae) is a polyphagous pest fruit fly for which the chemical profile of rectal glands is available for males but not for females. There have been no studies of the volatile emissions of either sex or of electrophysiological responses to these compounds. The present study (i) establishes the chemical profiles of rectal gland contents and volatiles emitted by both sexes of B. kraussi by gas chromatography–mass spectrometry (GC–MS) and (ii) evaluates the detection of the identified compounds by gas chromatography–electroantennogram detection (GC–EAD) and –electropalpogram detection (GC–EPD). Sixteen compounds are identified in the rectal glands of male B. kraussi and 29 compounds are identified in the rectal glands of females. Of these compounds, 5 were detected in the headspace of males and 13 were detected in the headspace of females. GC–EPD assays recorded strong signals in both sexes against (E,E)-2,8-dimethyl-1,7-dioxaspiro[5.5]undecane, 2-ethyl-7-mehtyl-1,6-dioxaspiro[4.5]decane isomer 2, (E,Z)/(Z,E)-2,8-dimethyl-1,7-dioxaspiro[5.5]undecane, and (Z,Z)-2,8-dimethyl-1,7-dioxaspiro[5.5]undecane. Male antennae responded to (E,E)-2,8-dimethyl-1,7-dioxaspiro[5.5]undecane, 2-methyl-6-pentyl-3,4-dihydro-2H-pyran, 6-hexyl-2-methyl-3,4-dihydro-2H-pyran, 6-oxononan-1-ol, ethyl dodecanoate, ethyl tetradecanoate and ethyl (Z)-hexadec-9-enoate, whereas female antennae responded to (E,E)-2,8-dimethyl-1,7-dioxaspiro[5.5]undecane and 2-methyl-6-pentyl-3,4-dihydro-2H-pyran only. These compounds are candidates as pheromones mediating sexual interactions in B. kraussi.
Formation of an N-formylkynurenine-derived fluorophore and its use for measuring indoleamine 2,3-dioxygenase 1 activity
Publisher: Springer Science and Business Media LLC
Date: 12-01-2013
DOI: 10.1007/S00216-012-6650-Y
Abstract: Indoleamine 2,3-dioxygenase 1 (IDO1) is a tryptophan-catabolizing enzyme whose expression by a broad range of clinical tumors is associated with immunosuppression and poor patient outcome. Here we describe a new fluorescence assay for measuring IDO1 activity suitable for high-throughput screening of compound libraries for novel IDO1 inhibitors. This assay is easy to perform, requiring the addition of only one reagent prior to readout. In place of measuring kynurenine, it uses the in situ formation of an N-formylkynurenine-derived fluorophore (NFKPIP) measured at an excitation wavelength of 400 nm and an emission wavelength of 500 nm. The fluorescence intensity of the NFKPIP formed is directly related to the amount of enzyme activity, and the signal is stable over 8 h. This assay has a lower limit of detection, equating to 153 nM N-formylkynurenine, which is over 30-fold lower than the limits of detection of existing assays for IDO1 activity. When we compared the performance of the new assay with that of the published colorimetric absorbance assay in screening the National Cancer Institute Diversity Set III of 1,597 compounds for IDO1 inhibitors, we obtained an identical list of the 25 most active compounds in the two assays. Although 93 compounds (aldehydes, ketones, and aromatic amines) in the library interfered with the absorbance readout, only 18 compounds (conjugated systems and fused cycles) interfered with the readout of the new fluorescence assay. IC(50) values determined using the new assay for three known IDO1 inhibitors-1,4-naphthoquinone, 4-amino-N-(3-chloro-4-fluorophenyl)-N'-hydroxy-1,2,5-oxadiazole-3-carboximidamide and 4-phenyl-1H-imidazole-were consistent with their literature values, further validating the new assay for measuring IDO1 activity.
Antimicrobial and antioxidant activity and chemical characterisation of Erythrina stricta Roxb. (Fabaceae)
Publisher: Elsevier BV
Date: 06-2016
DOI: 10.1016/J.JEP.2016.03.011
Abstract: The bark of Erythrina stricta Roxb. (Fabaceae) has been used in Indian indigenous systems as a remedy for rheumatism, stomach-ache, asthma, dysentery, contact dermatitis, eczema and skin infections. However, there have been limited phytochemical or biological studies on the bark of E. stricta and there are no studies that align with its traditional medicinal uses. The aim of this study was to assess the antimicrobial and antioxidant activity of the stem bark of E. stricta to support its topical use in the treatment of contact dermatitis, eczema and skin infections and to isolate and identify any bioactive compounds. MTT microdilution and disc diffusion assays were used to determine the antimicrobial activities of n-hexane, dichloromethane, ethyl acetate, methanol and water extracts of the bark of E. stricta. Column and preparative thin layer chromatography were used for the purification of the dichloromethane extract. The structures of the compounds isolated were elucidated by extensive 1D and 2D NMR spectroscopic techniques and comparison with published data. The antioxidant activities of the extracts were determined by DPPH free radical scavenging and FRAP assays and the antioxidant activity of the pure compounds by dot-blot and DPPH staining methods. The dichloromethane, ethyl acetate, and n-hexane extracts showed the most significant activity with MIC values of 7.8µg/mL, 125µg/mL, and 125µg/mL against a sensitive strain of Staphylococcus aureus. The dichloromethane and ethyl acetate extracts also showed significant activity against Candida albicans with MIC values of 125µg/mL and 1mg/mL respectively. GC-MS analysis of the n-hexane extract showed the presence of the antibacterial and antifungal compounds β-caryophyllene, caryophyllene oxide, α-selinene, β-selinene, selin-11-en-4-α-ol, α-copaene and δ-cadenine. Phytochemical studies of the dichloromethane extract led to the isolation of the novel compound erynone (1), together with six known compounds wighteone (2), alpinum isoflavone (3), luteone (4), obovatin (5), erythrinassinate B (6) and isovanillin (7). Luteone (4) exhibited the most significant antibacterial activity with minimum inhibitory quantity (MIQ) values of 1.88µg, 1.88µg and 3.75µg, respectively, against sensitive (MSSA) and resistant strains (MRSA and MDRSA) of S. aureus using a TLC bioautography assay. Erynone (1) exhibited the greatest DPPH free radical scavenging activity. Seven compounds, including a new chromanone, were isolated from the antimicrobial dichloromethane extract of the stem bark of E. stricta. Six of the seven compounds showed antibacterial and/or antioxidant activities. These findings provide support for the customary (traditional and contemporary) use of E. stricta bark for the treatment of skin and wound infections.
Methods to Enhance the Metabolic Stability of Peptide-Based PET Radiopharmaceuticals
Publisher: MDPI AG
Date: 14-05-2020
DOI: 10.3390/MOLECULES25102314
Abstract: The high affinity and specificity of peptides towards biological targets, in addition to their favorable pharmacological properties, has encouraged the development of many peptide-based pharmaceuticals, including peptide-based positron emission tomography (PET) radiopharmaceuticals. However, the poor in vivo stability of unmodified peptides against proteolysis is a major challenge that must be overcome, as it can result in an impractically short in vivo biological half-life and a subsequently poor bioavailability when used in imaging and therapeutic applications. Consequently, many biologically and pharmacologically interesting peptide-based drugs may never see application. A potential way to overcome this is using peptide analogues designed to mimic the pharmacophore of a native peptide while also containing unnatural modifications that act to maintain or improve the pharmacological properties. This review explores strategies that have been developed to increase the metabolic stability of peptide-based pharmaceuticals. It includes modifications of the C- and/or N-termini, introduction of d- or other unnatural amino acids, backbone modification, PEGylation and alkyl chain incorporation, cyclization and peptide bond substitution, and where those strategies have been, or could be, applied to PET peptide-based radiopharmaceuticals.
Ketimine reductase/CRYM catalyzes reductive alkylamination of α-keto acids, confirming its function as an imine reductase
Publisher: Springer Science and Business Media LLC
Date: 15-07-2015
DOI: 10.1007/S00726-015-2044-8
Abstract: Recently, crystalized mouse ketimine reductase/CRYM complexed with NADPH was found to have pyruvate bound in its active site. We demonstrate that the enzyme binds α-keto acids, such as pyruvate, in solution, and catalyzes the formation of N-alkyl-amino acids from alkylamines and α-keto acids (via reduction of imine intermediates), but at concentrations of these compounds not expected to be encountered in vivo. These findings confirm that, mechanistically, ketimine reductase/CRYM acts as a classical imine reductase and may explain the finding of bound pyruvate in the crystallized protein.
Rectal Gland Chemistry, Volatile Emissions, and Antennal Responses of Male and Female Banana Fruit Fly, Bactrocera musae
Publisher: MDPI AG
Date: 31-12-2019
Abstract: The banana fruit fly, Bactrocera musae (Tryon) (Diptera: Tephritidae), is an economically important pest endemic to Australia and mainland Papua New Guinea. The chemistry of its rectal glands, and the volatiles emitted during periods of sexual activity, has not been previously reported. Using gas chromatography–mass spectrometry (GC-MS), we find that male rectal glands contain ethyl butanoate, N-(3-methylbutyl) acetamide, ethyl laurate and ethyl myristate, with ethyl butanoate as the major compound in both rectal gland and headspace volatile emissions. Female rectal glands contain four major compounds, ethyl laurate, ethyl myristate, ethyl palmitate and (E,E)-2,8-dimethyl-1,7-dioxaspiro[5.5]undecane, as well as 11 minor compounds. For both male and female B. musae, all compounds found in the headspace were also present in the rectal gland extracts, suggesting that the rectal gland is the main source of the headspace volatiles. Gas chromatography–electroantennography (GC-EAD) of rectal gland extracts confirms that male antennae respond to male-produced ethyl laurate and female-produced (E,E)-2,8-dimethyl-1,7-dioxaspiro[5.5]undecane, while female antennae respond to male-produced ethyl butanoate but no female-produced compounds. This is an important step in understanding the volatiles involved in the chemical communication of B. musae, their functional significance, and potential application.
Expression and Purification of Recombinant Human Indoleamine 2,3-Dioxygenase
Publisher: Elsevier BV
Date: 06-2000
Modification of the fluorescein diacetate assay for screening of antifungal agents against Candida albicans: Comparison with the NCCLS methods
Publisher: Elsevier BV
Date: 08-2006
DOI: 10.1016/J.MIMET.2005.11.012
Abstract: A modified fluorescein diacetate (FDA) assay has been compared with standard NCCLS broth macrodilution and broth microdilution methods for the detection of antifungal activity. The FDA assay was performed in a medium containing bacteriological peptone, NaCl, yeast extract and glucose (0.2%, 0.1%, 0.1% and 1% w/v, respectively) and buffered with 10 mM BES buffer. The MICs of hotericin B, fluconazole, miconazole and flucytosine (representing three major classes of antifungal agents) obtained by the three methods were compared. The results obtained with the FDA assays correlated well with the NCCLS macrodilution method for MICs of hotericin B, miconazole and fluconazole, but not for flucytosine. However, the MIC values of flucytosine obtained with the FDA assay were well within the quality control range for the two reference strains recommended by the NCCLS. The FDA assay described is an attractive alternative to the NCCLS methods for screening for antifungal agents, with the added advantage of objectivity of fluorescence measurement.
Phytochemical Profile and Antibacterial and Antioxidant Activities of Medicinal Plants Used by Aboriginal People of New South Wales, Australia
Publisher: Hindawi Limited
Date: 2016
DOI: 10.1155/2016/4683059
Abstract: Aboriginal people of Australia possess a rich knowledge on the use of medicinal plants for the treatment of sores, wounds, and skin infections, ailments which impose a high global disease burden and require effective treatments. The antibacterial and antioxidant activities and phytochemical contents of extracts, obtained from eight medicinal plants used by Aboriginal people of New South Wales, Australia, for the treatment of skin related ailments, were assessed to add value to and provide an evidence-base for their traditional uses. Extracts of Acacia implexa , Acacia falcata , Cassytha glabella , Eucalyptus haemastoma , Smilax glyciphylla , Sterculia quadrifida , and Syncarpia glomulifera were evaluated. All extracts except that of S. quadrifida showed activity against sensitive and multidrug resistant strains of Staphylococcus aureus with minimum inhibitory concentration values ranging from 7.81 to 1000 μ g/mL. The sap of E. haemastoma and bark of A. implexa possessed high total phenolic contents (TPC) and strong DPPH radical scavenging abilities. A positive correlation was observed between TPC and free radical scavenging ability. GC-MS analysis of the n -hexane extract of S. glomulifera identified known antimicrobial compounds. Together, these results support the traditional uses of the examined plants for the treatment of skin related ailments and infections by Aboriginal people of New South Wales, Australia.
Lysine metabolism in mammalian brain: an update on the importance of recent discoveries
Publisher: Springer Science and Business Media LLC
Date: 17-09-2013
Is protein methylation in the human lens a result of non-enzymatic methylation by S-adenosylmethionine?
Publisher: Elsevier BV
Date: 06-2012
Kynurenine-3-monooxygenase: a review of structure, mechanism, and inhibitors
Publisher: Elsevier BV
Date: 02-2016
DOI: 10.1016/J.DRUDIS.2015.11.001
Abstract: Kynurenine monooxygenase (KMO) is an enzyme of the kynurenine (Kyn) pathway (KP), which is the major catabolic route of tryptophan. Kyn represents a branch point of the KP, being converted into the neurotoxin 3-hydroxykynurenine via KMO, neuroprotectant kynurenic acid, and anthranilic acid. As a result of this branch point, KMO is an attractive drug target for several neurodegenerative and/or neuroinflammatory diseases, especially Huntington's (HD), Alzheimer's (AD), and Parkinson's (PD) diseases. Although a neurological target, administration of KMO inhibitors in the periphery has demonstrated promising pharmacological results. In light of a recent crystal structure release and reports of preclinical candidates, here we provide a concise yet comprehensive update on the current state of research into the enzymology of KMO and related drug discovery efforts, highlighting areas where further work is required.
Macquarie–Yaegl Partnership: Community Capability Strengthening Through Western and Indigenous Science
Publisher: CSIRO Publishing
Date: 2021
DOI: 10.1071/CH20248
Abstract: The rich customary knowledge possessed by Indigenous people from around the world has provided intellectually stimulating academic research opportunities and has been a successful avenue for healthcare and drug discovery as well as commercial native foods, flavours, fragrances, nutraceuticals, cosmetics, and agricultural products. When conducted with benefit sharing and reciprocity as core agenda, such research can provide community capability strengthening and immense rewards for both the Indigenous people and the academic research team involved, as well as benefiting potentially many others. This account shares my experiences as a natural products and medicinal chemistry academic, of working with Australian Aboriginal Elders, most notably from Yaegl Country of northern New South Wales, on investigating their bush medicines. Together we have facilitated the recognition and preservation of Yaegl Country customary knowledge and through initiation of a science leadership program, the National Indigenous Science Education Program, we have promoted educational attainment and STEM engagement in Australian Aboriginal youth. While this account is authored as my own personal statement of the Macquarie–Yaegl partnership, I am indebted to the Yaegl Aboriginal Elders and other Australian Aboriginal people I have worked with, and my university, school and community collaborators, my research team and student volunteers, who have all enabled the outcomes described in this account to be realised, and have made the experience so rewarding. I am also thankful to the Royal Australian Chemical Institute for the recognition of the value of this work through the award of a 2019 Royal Australian Chemical Institute Citation.
Production of truncated enzymically active human indoleamine 2,3-dioxygenase using site-directed mutagenesis
Publisher: Elsevier BV
Date: 11-2002
Aboriginal medicinal plants of Queensland: ethnopharmacological uses, species diversity, and biodiscovery pathways
Publisher: Springer Science and Business Media LLC
Date: 10-08-2022
DOI: 10.1186/S13002-022-00552-6
Abstract: Aboriginal peoples have occupied the island continent of Australia for millennia. Over 500 different clan groups or nations with distinctive cultures, beliefs, and languages have learnt to live sustainably and harmoniously with nature. They have developed an intimate and profound relationship with the environment, and their use of native plants in food and medicine is largely determined by the environment they lived in. Over 1511 plant species have been recorded as having been used medicinally in Australia. Most of these medicinal plants were recorded from the Aboriginal communities in Northern Territory, New South Wales, South Australia, and Western Australia. Not much has yet been reported on Aboriginal medicinal plants of Queensland. Therefore, the main aim of this review is to collect the literature on the medicinal plants used by Aboriginal peoples of Queensland and critically assess their ethnopharmacological uses. The information used in this review was collected from archival material and uploaded into the Tropical Indigenous Ethnobotany Centre (TIEC) database. Archival material included botanist’s journals/books and old hard copy books. Scientific names of the medicinal plant species were matched against the ‘World Flora Online Plant List’, and ‘Australian Plant Census’ for currently accepted species names to avoid repetition. An oral traditional medical knowledge obtained through interviewing traditional knowledge holders (entered in the TIEC database) has not been captured in this review to protect their knowledge. This review identified 135 species of Queensland Aboriginal medicinal plants, which belong to 103 genera from 53 families, with Myrtaceae being the highest represented plant family. While trees represented the biggest habit, leaves were the most commonly used plant parts. Of 62 different diseases treated by the medicinal plants, highest number of plants are used for treating skin sores and infections. Few plants identified through this review can be found in other tropical countries but many of these medicinal plants are native to Australia. Many of these medicinal plants are also used as bush food by Aboriginal peoples. Through extensive literature review, we found that 135 medicinal plants native to Queensland are used for treating 62 different diseases, especially skin infections. Since these medicinal plants are also used as bush food and are rarely studied using the Western scientific protocols, there is a huge potential for bioprospecting and bush food industry.
Glutathione and NADH, but not Ascorbate, Protect Lens Proteins from Modification by UV Filters
Publisher: Elsevier BV
Date: 04-2002
An ethnobotanical study of medicinal plants of Chungtia village, Nagaland, India
Publisher: Elsevier BV
Date: 05-2015
DOI: 10.1016/J.JEP.2015.02.053
Abstract: Traditional medicinal plant knowledge is an integral and very important part of Indigenous cultures worldwide. For many communities there is a great urgency in recording this knowledge in written form. This is the first ethnobotanical report of medicinal plant knowledge of the Nagaland Ao tribe of Chungtia village and is an important step in the preservation of this culturally and medicinally significant knowledge. The aim of the presented work was to perform an ethnobotanical study on plants of medicinal and other significance to the Chungtia villagers of Nagaland, North East India. Ethnobotanical data were collected from traditional practitioners and Elders of Chungtia village by means of open group discussions and semi-structured interviews of groups and in iduals using questionnaires. The interviews were also recorded in an audio format in the local Mongsen language. The gathered ethnobotanical knowledge was compared with reported ethnobotanical usages worldwide and reported biological properties and phytochemical studies relevant to the Chungtia villagers׳ applications. A total of 135 plant species of 69 families and 123 genera were recorded for medicinal and household maintenance applications. Those applications were grouped into 13 categories based on Chungtia villagers׳ classification system. The families most represented were Asteraceae, Euphorbiaceae and Solanaceae. The most reported uses were for gastrointestinal problems, followed by dermatological problems. The most commonly used plant parts were leaves, followed by fruits and stems and they were most commonly administered as a paste, decoction, infusion, juice or poultice, or taken orally with no preparation. There was strong agreement among the informants as to the usages of the plants (informant consensus factor 0.80-0.91). The use value of 6 for Cassia floribunda, Dolichos lablab, Hedyotis scandens, Phyllanthus urinaria and Rhus javanica indicated these are the most important species. Forty four of the 135 plants had a fidelity level of 100%. This study has helped to document and preserve in written format important traditional plant knowledge of 135 plants of the Chungtia villagers, assisting them in the continued preservation of their cultural values.
Detection, Quantification, and Total Synthesis of Novel 3-Hydroxykynurenine Glucoside–Derived Metabolites Present in Human Lenses
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 10-02-2014
Abstract: 3-Hydroxykynurenine O-β-D-glucoside (3OHKG) protects the lens from UV damage, and novel related species may act analogously. The aim of this study was to detect, quantify, and elucidate the structures of novel 3-hydroxykynurenine glucoside-derived metabolites present in the human lens. Compounds were detected and quantified by liquid chromatography with tandem mass spectrometry (LC-MS/MS) in 24 human lenses of different ages, of which 22 were normal and two had cataract. Structures of these were confirmed through total synthesis. 3OHKG concentrations decreased with age in the lens nuclei, whereas the levels of three novel species, 4-(2-amino-3-hydroxyphenyl)-2-hydroxy-4-oxobutanoic acid O-β-D-glucoside (3OHKG-W), 3-hydroxykynurenine O-β-D-glucoside yellow (3OHKG-Y), and 2-amino-3-hydroxyacetophenone O-β-D-glucoside (AHAG), increased, though to different extents. In contrast, the concentrations present in the cortex of the lens remained constant with age. Three novel 3OHKG-derived metabolites have been detected in extracts from human lenses.
Role of Novel UV Filters in Human Lens Protein Damage Link to Age Related Nuclear Cataract
Publisher: Elsevier BV
Date: 2010
An Investigation into the In Vitro Metabolic Stability of Aryl Sulfonyl Fluorides for their Application in Medicinal Chemistry and Radiochemistry
Publisher: American Chemical Society (ACS)
Date: 13-01-2023
Identification of a new human lens UV filter compound
Publisher: Wiley
Date: 13-11-2001
DOI: 10.1016/S0014-5793(01)03102-7
Abstract: A new UV filter compound, 4-(2-amino-3-hydroxyphenyl)-4-oxobutanoic acid O-diglucoside, has been identified in human lenses. The structure suggests that it is a further metabolic product of the second most abundant UV filter compound, 4-(2-amino-3-hydroxyphenyl)-4-oxobutanoic acid O-glucoside. Quantification studies on the new compound show that it decreases towards zero in both the nucleus and cortex as a function of age. The discovery of this novel disaccharide completes the identification of the major UV filter compounds present in the human lens.
Reversible Binding of Kynurenine to Lens Proteins: Potential Protection by Glutathione in Young Lenses
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 08-2007
DOI: 10.1167/IOVS.06-1061
Abstract: Human ultraviolet light (UV) filters, such as kynurenine (Kyn), readily deaminate to reactive unsaturated ketones that covalently modify proteins in older human lenses. The aim of this study was to examine in vitro rates of formation and decomposition of the three major Kyn-amino acid adducts and possible consequences for the lens. The t-Boc-protected Kyn-His, Kyn-Lys, and Kyn-Cys adducts and Kyn-Cys were synthesized from the corresponding amino acids and Kyn. Calf lens proteins were modified with Kyn by incubation at pH 7. Stability and competition studies of the adducts were conducted under physiological conditions. Kyn-amino acids and their decomposition products were quantified using HPLC. At physiological pH, Kyn-Cys adducts formed more rapidly than either Lys or His adducts, but they also decomposed readily. By contrast, His adducts were stable. Cysteine (Cys) residues in beta-crystallins were major sites of modification. The Kyn moiety, initially bound to Cys residues, was found to transfer to other amino acids. Glutathione promoted the breakdown of Kyn-Cys. These data may help explain why proteins in young lenses are not modified by UV filters in situ. The initial phase of the modification of proteins in the human lens by UV filters may be a dynamic process. In lenses, Cys residues of crystallins modify preferentially, but these adducts also decompose to release deaminated Kyn. This can then potentially react with other amino acids. Glutathione, which is present in high concentrations in the lenses of young people, may play a vital role in keeping proteins free from modification by intercepting reactive deaminated kynurenines formed by the spontaneous breakdown of free UV filters, promoting the decomposition of Kyn-Cys residues, and sequestering the unsaturated ketones once they are released from modified proteins.
Identification of the new UV filter compound cysteine‐l ‐3‐hydroxykynurenine O‐β‐d ‐glucoside in human lenses
Publisher: Wiley
Date: 28-08-2006
DOI: 10.1016/J.FEBSLET.2006.08.026
Abstract: UV filters protect the human lens and retina from UV light-induced damage. Here, we report the identification of a new UV filter, cysteine-l-3-hydroxykynurenine O-beta-d-glucoside, which is present in older normal human lenses. Its structure was confirmed by independent synthesis. It is likely this novel UV filter is formed in the lens by nucleophilic attack of cysteine on the unsaturated ketone derived from deamination of 3-hydroxykynurenine O-beta-d-glucoside. Quantitation studies revealed considerable variation in normal lens levels that may be traced to the marked instability of the cysteine adduct. The novel UV filter was not detected in advanced nuclear cataract lenses.
Sampling technique biases in the analysis of fruit fly volatiles: a case study of Queensland fruit fly
Publisher: Springer Science and Business Media LLC
Date: 13-11-2020
DOI: 10.1038/S41598-020-76622-0
Abstract: Diverse methods have been used to s le insect semiochemicals. S ling methods can differ in efficiency and affinity and this can introduce significant biases when interpreting biological patterns. We compare common methods used to s le tephritid fruit fly rectal gland volatiles (‘pheromones’), focusing on Queensland fruit fly, Bactrocera tryoni . Solvents of different polarity, n -hexane, dichloromethane and ethanol, were compared using intact and crushed glands. Polydimethylsiloxane, polydimethylsiloxane/ inylbenzene and polyacrylate were compared as adsorbents for solid phase microextraction. Tenax-GR and Porapak Q were compared as adsorbents for dynamic headspace s ling. Along with compounds previously reported for B. tryoni , we detected five previously unreported compounds in males, and three in females. Dichloromethane extracted more amides while there was no significant difference between the three solvents in extraction of spiroacetals except for ( E , E )-2,8-dimethyl-1,7-dioxaspiro[5.5]undecane for which n -hexane extracted higher amount than both dichloromethane and ethanol. Ethanol failed to contain many of the more volatile compounds. Crushed rectal gland s les provided higher concentrations of extracted compounds than intact rectal gland s les, but no compounds were missed in intact s les. Of solid phase microextraction fibers, polyacrylate had low affinity for spiroacetals, ethyl isobutyrate and ethyl-2-methylbutanoate. Polydimethylsiloxane was more efficient for spiroacetals while type of fiber did not affect the amounts of amides and esters. In dynamic headspace s ling, Porapak was more efficient for ethyl isobutyrate and spiroacetals, while Tenax was more efficient for other esters and amides, and s ling time was a critical factor. Biases that can be introduced by s ling methods are important considerations when collecting and interpreting insect semiochemical profiles.
Imine Reductases: A Comparison of Glutamate Dehydrogenase to Ketimine Reductases in the Brain
Publisher: Springer Science and Business Media LLC
Date: 12-01-2013
Insights into Enzyme Catalysis and Thyroid Hormone Regulation of Cerebral Ketimine Reductase/μ-Crystallin Under Physiological Conditions
Publisher: Springer Science and Business Media LLC
Date: 05-2015
DOI: 10.1007/S11064-015-1590-5
Abstract: Mammalian ketimine reductase is identical to μ-crystallin (CRYM)-a protein that is also an important thyroid hormone binding protein. This dual functionality implies a role for thyroid hormones in ketimine reductase regulation and also a reciprocal role for enzyme catalysis in thyroid hormone bioavailability. In this research we demonstrate potent sub-nanomolar inhibition of enzyme catalysis at neutral pH by the thyroid hormones L-thyroxine and 3,5,3'-triiodothyronine, whereas other thyroid hormone analogues were shown to be far weaker inhibitors. We also investigated (a) enzyme inhibition by the substrate analogues pyrrole-2-carboxylate, 4,5-dibromopyrrole-2-carboxylate and picolinate, and (b) enzyme catalysis at neutral pH of the cyclic ketimines S-(2-aminoethyl)-L-cysteine ketimine (owing to the complex nomenclature trivial names are used for the sulfur-containing cyclic ketimines as per the original authors' descriptions) (AECK), Δ(1)-piperideine-2-carboxylate (P2C), Δ(1)-pyrroline-2-carboxylate (Pyr2C) and Δ(2)-thiazoline-2-carboxylate. Kinetic data obtained at neutral pH suggests that ketimine reductase/CRYM plays a major role as a P2C/Pyr2C reductase and that AECK is not a major substrate at this pH. Thus, ketimine reductase is a key enzyme in the pipecolate pathway, which is the main lysine degradation pathway in the brain. In silico docking of various ligands into the active site of the X-ray structure of the enzyme suggests an unusual catalytic mechanism involving an arginine residue as a proton donor. Given the critical importance of thyroid hormones in brain function this research further expands on our knowledge of the connection between amino acid metabolism and regulation of thyroid hormone levels.
Novel human lens metabolites from normal and cataractous human lenses
Publisher: Elsevier BV
Date: 06-2007
CMKb: a web-based prototype for integrating Australian Aboriginal customary medicinal plant knowledge
Publisher: Springer Science and Business Media LLC
Date: 12-2008
DOI: 10.1186/1471-2105-9-S12-S25
Abstract: The customary medicinal plant knowledge possessed by the Australian Aboriginal people is a significant resource. Published information on it is scattered throughout the literature, in heterogeneous data formats, and is scattered among various Aboriginal communities across Australia, due to a multiplicity of languages. This ancient knowledge is at risk due to loss of bio ersity, cultural impact and the demise of many of its custodians. We have developed the Customary Medicinal Knowledgebase (CMKb), an integrated multidisciplinary resource, to document, conserve and disseminate this knowledge. CMKb is an online relational database for collating, disseminating, visualising and analysing initially public domain data on customary medicinal plants. The database stores information related to taxonomy, phytochemistry, biogeography, biological activities of customary medicinal plant species as well as images of in idual species. The database can be accessed at mkb . Known bioactive molecules are characterized within the chemoinformatics module of CMKb, with functions available for molecular editing and visualization. CMKb has been developed as a prototype data resource for documenting, integrating, disseminating, analysing multidisciplinary customary medicinal plant data from Australia and to facilitate user-defined complex querying. Each species in CMKb is linked to online resources such as the Integrated Taxonomic Information System (ITIS), NCBI Taxonomy, Australia's SpeciesLinks-Integrated Botanical Information System (IBIS) and Google images. The bioactive compounds are linked to the PubChem database. Overall, CMKb serves as a single knowledgebase for holistic plant-derived therapeutics and can be used as an information resource for bio ersity conservation, to lead discovery and conservation of customary medicinal knowledge.
Protein-bound kynurenine is a photosensitizer of oxidative damage
Publisher: Elsevier BV
Date: 11-2004
Mutation of cysteine residues alters the heme-binding pocket of indoleamine 2,3-dioxygenase-1
Publisher: Elsevier BV
Date: 07-2013
DOI: 10.1016/J.BBRC.2013.05.119
Abstract: The hemoprotein indoleamine 2,3-dioxygenase-1 (IDO1) is the first and rate-limiting enzyme in mammalian tryptophan metabolism. Interest in IDO1 continues to grow, due to the ever expanding influence IDO1 plays in the immune response. This study examined the contribution of all in idual cysteine residues towards the overall catalytic properties and stability of recombinant human IDO1 via mutagenesis studies using a range of biochemical and spectroscopic techniques, including in vitro kinetic assessment, secondary structure identification via circular dichroism spectroscopy and thermal stability assessment. Upon mutation of cysteine residues we observed changes in secondary structure (principally, shifting from α-helix/β-sheet features to random coil structures) that produced out of plane heme torsion and puckering, changes to thermal stability (including gains in stability for one mutant protein) and differences in enzymatic activity (such as, increased ability to convert non-natural substrates, e.g.d-tryptophan) from wild type IDO1 enzyme.
Carborane-Containing Hydroxyamidine Scaffolds as Novel Inhibitors of Indoleamine 2,3-Dioxygenase 1 (IDO1)
Publisher: CSIRO Publishing
Date: 2015
DOI: 10.1071/CH15489
Abstract: Two new carborane-containing hydroxyamidines were prepared as potential inhibitors of the indoleamine 2,3-dioxygenase 1 (IDO1) enzyme. One compound (3) displayed low micromolar (1.90 μM) inhibition of IDO1, with the related compound (4) displaying -fold lower inhibitory activity, i.e. subtle differences in structure between the two carborane compounds led to dramatic changes in inhibitor binding. In silico docking experiments unravel a possible molecular mechanism that is consistent with the observed difference in IDO1 binding for 3 and 4 and also for the phenyl bioisosteres 1 and 2.
A fluorescence-based assay for indoleamine 2,3-dioxygenase
Publisher: Elsevier BV
Date: 02-2006
Abstract: A rapid and sensitive fluorescence-based bioassay for determination of indoleamine 2,3-dioxygenase (IDO) activity has been developed. This assay relies on the quantification of the amount of kynurenine produced in the assay medium by fluorescence and complements the standard absorbance and high-performance liquid chromatography (HPLC) assay methods. The fluorescence method has limits of detection similar to those of the standard assay methods. Measured activities of IDO, including in the presence of tryptophan-based inhibitors, were in statistical agreement with the absorbance and HPLC assay methods. The fluorescence-based assay was also suitable for assessment of IDO inhibition by compounds that are incompatible with the absorbance method.
An Ethnopharmacological Study of Medicinal Plants in New South Wales
Publisher: MDPI AG
Date: 30-10-2005
DOI: 10.3390/10101252
Regulation of Indoleamine 2,3-Dioxygenase, The First Enzyme in Uv Filter Biosynthesis in the Human Lens
Publisher: Springer US
Date: 1999
DOI: 10.1007/978-1-4615-4709-9_31
Abstract: 3-Hydroxykynurenine (3OHKyn), the precursor of UV filters in human lens, is highly autooxidizable, generates H2O2, and binds to lens proteins, yielding a tanned/yellow product resembling senile nuclear cataractous materials. Thus, if 3OHkyn can be shown to be the causative agent in cataract, it may be possible to prevent the disease by lowering the level of 3OHKyn. To this end, indoleamine 2,3-dioxygenase, the first enzyme in UV filter synthesis, was studied using lens epithelial cell lines. The results indicated that the IDO expression is mediated by IFN-gamma. Immuno-suppressants which inhibit production of IFN-gamma may act as anti-cataract agents. Another way to lower the level of 3OHKyn is to use specific inhibitors for IDO. A recombinant human IDO was expressed to develop the inhibitors.
Bactericidal and cyclooxygenase inhibitory diterpenes from Eremophila sturtii
Publisher: Elsevier BV
Date: 06-2006
DOI: 10.1016/J.PHYTOCHEM.2006.04.014
Abstract: Two serrulatane diterpenes, 3,8-dihydroxyserrulatic acid (1) and serrulatic acid (2), have been isolated from Eremophila sturtii through bioassay-guided fractionation. These compounds inhibit the inflammation pathway enzymes cyclooxygenase 1 and 2, and exhibit bactericidal activity against Staphylococcus aureus.
Novel indoleamine 2,3-dioxygenase-1 inhibitors from a multistep in silico screen
Publisher: Elsevier BV
Date: 02-2012
DOI: 10.1016/J.BMC.2011.10.068
Abstract: Indoleamine 2,3-dioxygenase-1 (IDO-1) is a heme containing enzyme that catalyses the initial step in the major pathway of l-tryptophan catabolism the kynurenine pathway. A large body of evidence has been accumulating for its immunosuppressive and tumoural escape roles and its applicability as a therapeutic target. Of particular interest is the possibility that IDO-1 inhibition may arrest, and sometimes revert, tumour growth. There exists a continuing need for the development of new and specific inhibitors for IDO-1, and we have created three pharmacophores designed to aid in this search. Initial database hits were further screened using Kier flexibility and a 'What-If' docking technique, designed to overcome the inherent limitations of today's forcefields with regards to heme chemistry. Eighteen compounds were tested in vitro, yielding four novel inhibitors with low micromolar IC(50) values, comparable with current inhibitors.
Bioactivity and chemical characterisation of Lophostemon suaveolens – an endemic Australian Aboriginal traditional medicinal plant
Publisher: Informa UK Limited
Date: 05-05-2015
DOI: 10.1080/14786419.2015.1038260
Abstract: Lophostemon suaveolens is a relatively unexplored endemic medicinal plant of Australia. Extracts of fresh leaves of L. suaveolens obtained from sequential extraction with n-hexane and dichloromethane exhibited antibacterial activity in the disc diffusion and MTT microdilution assays against Streptococcus pyogenes and methicillin sensitive and resistant strains of Staphylococcus aureus (minimum bactericidal concentration < 63 μg/mL). The dichloromethane extract and chromatographic fractions therein inhibited nitric oxide in RAW264.7 murine macrophages (IC50 3.7-11.6 μg/mL) and also PGE2 in 3T3 murine fibroblasts (IC50 2.8-19.7 μg/mL). The crude n-hexane, dichloromethane and water extracts of the leaves and chromatographic fractions from the dichloromethane extract also showed modest antioxidant activity in the ORAC assay. GC-MS analysis of the n-hexane fraction showed the presence of the antibacterial compounds aromadendrene, spathulenol, β-caryophyllene, α-humulene and α-pinene and the anti-inflammatory compounds β-caryophyllene and spathulenol. Fractionation of the dichloromethane extract led to the isolation of eucalyptin and the known anti-inflammatory compound betulinic acid.
Optimised expression and purification of recombinant human indoleamine 2,3-dioxygenase
Publisher: Elsevier BV
Date: 10-2004
Antimicrobial activity of customary medicinal plants of the Yaegl Aboriginal community of northern New South Wales, Australia: a preliminary study
Publisher: Springer Science and Business Media LLC
Date: 30-06-2015
Tryptophan-derived ultraviolet filter compounds covalently bound to lens proteins are photosensitizers of oxidative damage
Publisher: Elsevier BV
Date: 03-2008
DOI: 10.1016/J.FREERADBIOMED.2007.12.003
Abstract: The human eye is chronically exposed to light of wavelengths >300 nm. In the young human lens, light of wavelength 300-400 nm is predominantly absorbed by the free Trp derivatives kynurenine (Kyn), 3-hydroxykynurenine (3OHKyn), and 3-hydroxykynurenine-O-beta-D-glucoside (3OHKynG). These ultraviolet (UV) filter compounds are poor photosensitizers. With age, the levels of the free UV filters in the lens decreases and those of protein-bound UV filters increases. The photochemical behavior of these protein-bound UV filters and their role in UV damage are poorly elucidated and are examined here. UVA illumination of protein-bound UV filters generated peroxides (principally H2O2) in a metabolite-, photolysis-time-, and wavelength-dependent manner. Unmodified proteins, free Trp metabolites, and Trp metabolites that do not bind to lens proteins gave low peroxide yields. Protein-bound 3OHKyn (principally at Cys residues) yielded more peroxide than comparable Kyn and 3OHKynG adducts. Studies using D2O and sodium azide implicated 1O2 as a key intermediate. Illumination of the protein-bound adducts also yielded protein-bound Tyr oxidation products (DOPA, di-tyrosine) and protein cross-links via alternative mechanisms. These data indicate that the covalent modification of lens proteins by Kyn derivatives yields photosensitizers that may enhance oxidation in older lenses and contribute to age-related nuclear cataract.
Synthesis of Human Ultraviolet Filter Compounds: O-β-d -Glucopyranosides of 3-Hydroxykynurenine and 2-Amino-3-hydroxy-γ-oxobenzenebutanoic Acid
Publisher: American Chemical Society (ACS)
Date: 05-1999
DOI: 10.1021/JO982321N
Age‐dependent modification of proteins: N‐terminal racemization
Publisher: Wiley
Date: 20-03-2013
DOI: 10.1111/FEBS.12217
Abstract: Age-dependent deterioration of long-lived proteins in humans may have wide-ranging effects on health, fitness and diseases of the elderly. To a large extent, denaturation of old proteins appears to result from the intrinsic instability of certain amino acids however, these reactions are incompletely understood. One method to investigate these reactions involves exposing peptides to elevated temperatures at physiological pH. Incubation of PFHSPSY, which corresponds to a region of human αB-crystallin that is susceptible to age-related modification, resulted in the appearance of a major product. NMR spectroscopy confirmed that this novel peptide formed via racemization of the N-terminal Pro. This phenomenon was not confined to Pro, because peptides with N-terminal Ser and Ala residues also underwent racemization. As N-terminal racemization occurred at 37 °C, a long-lived protein was examined. LC-MS/MS analysis revealed that approximately one third of aquaporin 0 polypeptides in the centre of aged human lenses were racemized at the N-terminal methionine.
The role of natural products chemistry in the capability strengthening of Indigenous communities
Publisher: Georg Thieme Verlag KG
Date: 14-12-2016
Synthesis of exogonic acid and related compounds
Publisher: American Chemical Society (ACS)
Date: 04-1989
DOI: 10.1021/JO00270A031
Discovery and characterisation of hydrazines as inhibitors of the immune suppressive enzyme, indoleamine 2,3-dioxygenase 1 (IDO1)
Publisher: Elsevier BV
Date: 12-2013
DOI: 10.1016/J.BMC.2013.10.037
Abstract: Screening of a fragment library identified 2-hydrazinobenzothiazole as a potent inhibitor of indoleamine 2,3-dioxygenase 1 (IDO1), an enzyme expressed by tumours that suppresses the immune system. Spectroscopic studies indicated that 2-hydrazinobenzothiazole interacted with the IDO1 haem and in silico docking predicted that the interaction was through hydrazine. Subsequent studies of hydrazine derivatives identified phenylhydrazine (IC50=0.25 ± 0.07 μM) to be 32-fold more potent than 2-hydrazinobenzothiazole (IC50=8.0 ± 2.3 μM) in inhibiting rhIDO1 and that it inhibited cellular IDO1 at concentrations that were noncytotoxic to cells. Here, phenylhydrazine is shown to inhibit IDO1 through binding to haem.
Separate mechanisms for age-related truncation and racemisation of peptide-bound serine
Publisher: Springer Science and Business Media LLC
Date: 05-12-2013
DOI: 10.1007/S00726-013-1619-5
Abstract: Some amino acids are particularly susceptible to degradation in long-lived proteins. Foremost among these are asparagine, aspartic acid and serine. In the case of serine residues, cleavage of the peptide bond on the N-terminal side, as well as racemisation, has been observed. To investigate the role of the hydroxyl group, and whether cleavage and racemisation are linked by a common mechanism, serine peptides with a free hydroxyl group were compared to analogous peptides where the serine hydroxyl group was methylated. Peptide bond cleavage adjacent to serine was increased when the hydroxyl group was present, and this was particularly noticeable when it was present as the hydroxide ion. Adjacent amino acid residues also had a pronounced affect on cleavage at basic pH, with the SerPro motif being especially susceptible to scission. Methylation of the serine hydroxyl group abolished truncation, as did insertion of a bulky amino acid on the N-terminal side of serine. By contrast, racemisation of serine occurred to a similar extent in both O-methylated and unmodified peptides. On the basis of these data, it appears that racemisation of Ser, and cleavage adjacent to serine, occur via separate mechanisms. Addition of water across the double bond of dehydroalanine was not detected, suggesting that this mechanism was unlikely to be responsible for conversion of L-serine to D-serine. Abstraction of the alpha proton may account for the majority of racemisation of serine in proteins.
The genus Alphitonia Reissek ex Endl. (Rhamnaceae): A review of its customary uses, phytochemistry and biological activities
Publisher: Elsevier BV
Date: 08-2022
DOI: 10.1016/J.JEP.2022.115168
Abstract: Alphitonia Reissek ex Endl. is a relatively small genus of the family Rhamnaceae. Plants of this genus are found predominantly in the tropical regions of Southeast Asia, Australia and the Pacific, with some species being widely distributed and others endemic to a region. Almost half of the species of the Alphitonia genus have been reported for their customary (traditional and contemporary) medicinal uses. This includes for the treatment of skin conditions, headache, stomachache, inflammation, and body pain such as joint pain and childbirth. The aim of this review is to provide the first comprehensive account on the customary uses including ethnomedicinal uses, and phytochemistry and biological activities of the Alphitonia genus, and to identify gaps in current knowledge and scope for future research of plants of this genus. Information relevant to the genus Alphitonia was collected by searching the scientific databases (SciFinder, Google Scholar, ACS publications, PubMed, Wiley Online Library and International Plant name Index). Species names were validated using the World Flora Online database (www.worldfloraonline.org). Eight plants from the Alphitonia genus have been reported to be used as customary medicines, i.e. A. excelsa, A. ferruginea, A. franguloides, A. incana, A. neocaledonica, A. petriei, A. philippinensis and A. zizyphoides. A. excelsa, A. petriei, A. philippinensis and A. zizyphoides, have been shown to have biological activities that align with their customary uses, including antimicrobial, antioxidant and anti-inflammatory activities. Only five Alphitonia species reported for their medicinal customary uses have been explored for their phytochemistry, i.e. A. excelsa, A. neocaledonica, A. petriei, A. philippinensis and A. zizyphoides. Compounds identified from these plants include those that are well known for their medicinal importance. A. macrocarpa, A. whitei and A. xerocarpus have also been examined for their phytochemistry and have been found to have the same or similar bioactive compounds to those found in customarily used Alphitonia species. No biological activities or phytochemistry studies have been reported for the known customarily used medicinal plants A. ferruginea, A. franguloides and A. incana. This review highlights the customary uses, biological activities and phytochemistry of plants of the Alphitonia Reissek ex Endl. genus and highlights the significance of the knowledge systems of Indigenous peoples. Of the plants that have been researched for their biological activities and phytochemistry, there is good correlation with these properties and their customary medicinal uses. However, over half of the plants of the Alphitonia genus, including those that are already reported in the public domain for their customary medicinal uses, have had none or limited biological activities or phytochemistry studies conducted. While only eight species of the Alphitonia genus have been reported as customary medicines, other Alphitonia species also possess medicinally important compounds, and it is possible that they are customary medicines but their uses have not been shared publicly by the Indigenous knowledge custodians. There is clearly much scope for further investigation of this genus with regards to their ethnomedicinal uses and therapeutic potential.
Two oleanane triterpenoids from Gordonia ceylanica and their conversions to taraxarane triterpenoids
Publisher: Elsevier BV
Date: 08-2000
DOI: 10.1016/S0031-9422(00)00037-6
Abstract: Chemical investigation of the hot hexane extract of the stem bark of Gordonia ceylanica afforded two new oleanane triterpenoids, 3beta-acetoxy-11alpha, 13beta-dihydroxyolean-12-one and 3beta,11alpha-diacetoxy-13beta-hydroxyolean-12-one (2) The attempted acid hydrolysis of these two compounds resulted the dehydration and subsequent methyl group migration to afford the taraxarane triterpenoids 3beta,11alpha-dihydroxytaraxer-14-en-12-one (4) and 3beta-hydroxy-11alpha-acetoxytaraxer-14-en-12-one (5), respectively. These taraxaranes have not been previously reported.
Systematic Modification of Zingerone Reveals Structural Requirements for Attraction of Jarvis’s Fruit Fly
Publisher: Springer Science and Business Media LLC
Date: 18-12-2019
DOI: 10.1038/S41598-019-55778-4
Abstract: Tephritid fruit flies are amongst the most significant horticultural pests globally and male chemical lures are important for monitoring and control. Zingerone has emerged as a unique male fruit fly lure that can attract dacine fruit flies that are weakly or non-responsive to methyl eugenol and cuelure. However, the key features of zingerone that mediate this attraction are unknown. As Jarvis’s fruit fly, Bactrocera jarvisi (Tryon), is strongly attracted to zingerone, we evaluated the response of B. jarvisi to 37 zingerone analogues in a series of field trials to elucidate the functional groups involved in attraction. The most attractive analogues were alkoxy derivatives, with isopropoxy being the most attractive, followed by ethoxy and trifluoromethoxy analogues. All of the phenolic esters tested were also attractive with the response typically decreasing with increasing size of the ester. Results indicate that the carbonyl group, methoxy group, and phenol of zingerone are key sites for the attraction of B. jarvisi and identify some constraints on the range of structural modifications that can be made to zingerone without compromising attraction. These findings are important for future work in developing and optimising novel male chemical lures for fruit flies.
Optimisation of the fluorescein diacetate antibacterial assay
Publisher: Elsevier BV
Date: 2005
DOI: 10.1016/J.MIMET.2004.08.010
Abstract: The fluorescein diacetate (FDA) antibacterial assay relies on the cleavage of fluorescein diacetate by metabolically active bacteria. The recent finding that microbiological media can lead to significant levels of cleavage has reduced the reliability of the assay. Using the nucleophilic scavengers N-ethylmaleimide and maleic anhydride, we have demonstrated that this abiotic cleavage is most likely due to nucleophiles such as cysteine and histidine commonly present in the media. To increase the reliability of the assay we have modified the original assay conditions to include use of dilute medium (peptone 0.2% w/v, yeast extract 0.1% w/v and NaCl 0.1% w/v) in a non-nucleophilic buffer and overnight incubation of the medium after addition of antibacterial agents. The optimised fluorescein diacetate assay has been used to determine the MIC of gentamicin, tetracycline and chlor henicol for Escherichia coli, Staphyloccocus aureus and Pseudomonas aeruginosa and gave quantitative results that were reproducible and consistent with published data.
Isoflavonoids and a pterocarpan from Gliricidia sepium
Publisher: Elsevier BV
Date: 1998
Attraction and Electrophysiological Response to Identified Rectal Gland Volatiles in Bactrocera frauenfeldi (Schiner)
Publisher: MDPI AG
Date: 11-03-2020
DOI: 10.3390/MOLECULES25061275
Abstract: Bactrocera frauenfeldi (Schiner) (Diptera: Tephritidae) is a polyphagous fruit fly pest species that is endemic to Papua New Guinea and has become established in several Pacific Islands and Australia. Despite its economic importance for many crops and the key role of chemical-mediated sexual communication in the reproductive biology of tephritid fruit flies, as well as the potential application of pheromones as attractants, there have been no studies investigating the identity or activity of rectal gland secretions or emission profiles of this species. The present study (1) identifies the chemical profile of volatile compounds produced in rectal glands and released by B. frauenfeldi, (2) investigates which of the volatile compounds elicit an electroantennographic or electropalpographic response, and (3) investigates the potential function of glandular emissions as mate-attracting sex pheromones. Rectal gland extracts and headspace collections from sexually mature males and females of B. frauenfeldi were analysed by gas chromatography-mass spectrometry. Male rectal glands contained (E,E)-2-ethyl-8-methyl-1,7-dioxaspiro [5.5]undecane as a major component and (E,E)-2,8-dimethyl-1,7-dioxaspiro[5.5]undecane as a moderate component. Minor components included palmitoleic acid, palmitic acid, and ethyl oleate. In contrast, female rectal glands contained (E,E)-2,8-dimethyl-1,7-dioxaspiro[5.5]undecane and ethyl laurate as major components, ethyl myristate and ethyl palmitoleate as moderate components, and 18 minor compounds including amides, esters, and spiroacetals. Although fewer compounds were detected from the headspace collections of both males and females than from the gland extractions, most of the abundant chemicals in the rectal gland extracts were also detected in the headspace collections. Gas chromatography coupled electroantennographic detection found responses to (E,E)-2,8-dimethyl-1,7-dioxaspiro[5.5]undecane from the antennae of both male and female B. frauenfeldi. Responses to (E,E)-2-ethyl-8-methyl-1,7-dioxaspiro[5.5]undecane were elicited from the antennae of females but not males. The two spiroacetals also elicited electropalpographic responses from both male and female B. frauenfeldi. Ethyl caprate and methyl laurate, found in female rectal glands, elicited responses in female antennae and palps, respectively. Y-maze bioassays showed that females were attracted to the volatiles from male rectal glands but males were not. Neither males nor females were attracted to the volatiles from female rectal glands. Our findings suggest (E,E)-2,8-dimethyl-1,7-dioxaspiro[5.5]undecane and (E,E)-2-ethyl-8-methyl-1,7-dioxaspiro[5.5]undecane as components of a sex-attracting pheromone in B. frauenfeldi.
Mercury(II)-mediated routes to some side-chain functionalised 1,7-dioxaspiro[5.5]undecanes. Applications of Luche-Barbier chemoselective addition to ketoaldehydes
Publisher: Elsevier BV
Date: 03-1991
Antibacterial compounds from Carissa lanceolata R.Br.
Publisher: Elsevier BV
Date: 11-2000
DOI: 10.1016/S0031-9422(00)00343-5
Abstract: The dichloromethane extract of the wood of Carissa lanceolata R.Br. (Apocynaceae) afforded the eudesmanes carissone, dehydrocarissone and carindone. This is the first account of carissone being isolated from the wood of C. lanceolata, and of carindone being isolated from this Carissa species. Dehydrocarissone has not been isolated previously from any Carissa species. The antibacterial activity of these natural products were examined against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. All three compounds showed activity, with dehydrocarissone and carindone having a minimum inhibitory concentration less than 0.5 mg/ml against S. aureus and E. coli.
An ethnobotanical study of medicinal plants used by the Yaegl Aboriginal community in northern New South Wales, Australia
Publisher: Elsevier BV
Date: 2012
DOI: 10.1016/J.JEP.2011.11.008
Abstract: Documentation of Australian bush medicines is of utmost importance to the preservation of this disappearing and invaluable knowledge. This collaboration between the Yaegl Aboriginal community in northern New South Wales (NSW), Australia and an academic institution, demonstrates an effective means of preserving and adding value to this information. Questionnaire-guided interviews were performed with community Elders under a framework of participatory action research. Medicinal plant knowledge was collated in a handbook to aid interviews and to be used as an ongoing resource by the community. Specimens for all non-cultivar plants that were discussed were collected and deposited in herbaria with unique voucher numbers. This medicinal knowledge was checked against the literature for reports of related use and studies of biological activity. Nineteen Elders were interviewed, leading to discussions on fifty four plant preparations used for medicinal purposes. These plant preparations involved thirty two plants coming from twenty one families, reflecting the botanical ersity of the area. The plants retained in the Yaegl pharmacopoeia correspond to their accessibility and ease of preparation, reflected in their ongoing utilisation. Several plant uses did not appear elsewhere in the literature. This study is the first comprehensive documentation of the medicinal knowledge of the Yaegl Aboriginal community. It has been conducted using participatory action research methods and adds to the recorded customary knowledge of the region. The customary medicinal knowledge retained by the Yaegl Aboriginal community is related to the evolving needs of the community and accessibility of plants.
Ancient indian document analysis using cognitive memory network
Publisher: IEEE
Date: 09-2014
Cross-linking of lens crystallin proteins induced by tryptophan metabolites and metal ions: implications for cataract development
Publisher: Informa UK Limited
Date: 27-07-2016
DOI: 10.1080/10715762.2016.1210802
Abstract: Long-wavelength solar UV radiation is implicated in photodamage to the human eye. The human lens contains multiple tryptophan-derived compounds that have significant absorbance bands in the UVA region (λ 315-400 nm) that act as efficient physical filters for these wavelengths. The concentrations of many of these UV filter compounds decrease with increase in age, resulting in diminished protection, increased oxidative damage and the accumulation of modified proteins implicated in nuclear cataract formation. This damage may arise via the formation of α,β-unsaturated carbonyls from the UV filter compounds, adduction to lens proteins and subsequent action as photosensitizers, and/or via the reactions of redox-active transition metal ions that accumulate in aged human lenses. The latter may promote the oxidation of free, or protein-bound, o-aminophenols, such as the UV filter compounds 3-hydroxykynurenine (3OHKyn) and 3-hydroxyanthranilic acid (3OHAA). It is shown here that Cu(II), and to a lesser extent Fe(III), enhance oxidation of free 3OHKyn, 3OHAA and 3OHKyn bound to specific amino acids and lens proteins, with this resulting in increased cross-linking of lens proteins. These data indicate that elevated levels of transition metal ions in aging lenses can enhance the loss of protective UV filter compounds, and contribute to the formation of high-molecular-mass dysfunctional crystallin proteins in a light-independent manner. These reactions may contribute to the formation of lens cataracts in humans.
The River of Learning: building relationships in a university, school and community Indigenous widening participation collaboration
Publisher: Informa UK Limited
Date: 11-05-2017
The first indoleamine-2,3-dioxygenase-1 (IDO1) inhibitors containing carborane
Publisher: Royal Society of Chemistry (RSC)
Date: 2014
DOI: 10.1039/C4DT00444B
Abstract: The first ex les of indoleamine-2,3-dioxygenase-1 (IDO1) inhibitors containing a carborane cage are reported.
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