ORCID Profile
0000-0003-2699-6603
Current Organisations
Royal Brisbane and Women's Hospital
,
The Eye Health Centre
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Publisher: Elsevier BV
Date: 11-2007
Publisher: Elsevier BV
Date: 06-2006
Publisher: Wiley
Date: 28-08-2014
DOI: 10.1111/CEO.12385
Publisher: S. Karger AG
Date: 10-02-2017
DOI: 10.1159/000456652
Abstract: Acanthosis nigricans (AN) is a dermatopathy associated with insulin-resistance, drugs, endocrine disorders, chromosomal abnormalities (benign AN), and neoplasia (malignant AN). Malignant AN (MAN) is a rare paraneoplastic skin syndrome most commonly associated with gastric adenocarcinoma and other intra-abdominal malignancies. We report the case of a 28-year-old female with AN associated with obesity, insulin resistance, and endometrial adenocarcinoma. Although rare, MAN is often an initial sign of malignancy and must trigger extensive investigation, particularly in patients with sudden development of possibly paraneoplastic dermatoses or in patients diagnosed with benign AN with any atypical features.
Publisher: Informa UK Limited
Date: 08-2014
DOI: 10.2147/OPTH.S64248
Publisher: American Chemical Society (ACS)
Date: 09-01-2018
DOI: 10.1021/PR0705136
Abstract: The increasing use of multistage tandem mass spectrometry (MS/MS and MS (3)) methods for comprehensive phosphoproteome analysis studies, as well as the emerging application of in silico spectral intensity prediction algorithms in enhanced database search analysis strategies, necessitate the development of an improved understanding of the mechanisms and other factors that affect the gas-phase fragmentation reactions of phosphorylated peptide ions. To address this need, we have examined the multistage collision-induced dissociation (CID) behavior of a set of singly and doubly charged phosphoserine- and phosphothreonine-containing peptide ions, as well as their regioselectively or uniformly deuterated derivatives, in a quadrupole ion trap mass spectrometer. Consistent with previous reports, the neutral loss of phosphoric acid (H 3PO 4) was observed as a dominant reaction pathway upon MS/MS. The magnitude of this loss was found to be highly dependent on the proton mobility of the precursor ion for both phosphoserine- and phosphothreonine-containing peptides. In contrast to that currently accepted in the literature, however, the results obtained in this study unequivocally demonstrate that the loss of H 3PO 4 does not predominantly occur via a "charge-remote" beta-elimination reaction. The observation of product ions corresponding to the loss of formaldehyde (CH 2O, 30 Da, or CD 2O, 32 Da) or acetaldehyde (CH 3CHO, 44 Da) upon MS (3) dissociation of the [M+ nH-H 3PO 4] ( n+ ) product ions from phosphoserine- and phosphothreonine-containing peptide ions, respectively, provide experimental evidence for a "charge-directed" mechanism involving an S N2 neighboring group participation reaction, resulting in the formation of a cyclic product ion. Potentially, these "diagnostic" MS (3) product ions may provide additional information to facilitate the characterization of phosphopeptides containing multiple potential phosphorylation sites.
Publisher: Springer Science and Business Media LLC
Date: 2013
Publisher: Royal Society of Chemistry (RSC)
Date: 2006
DOI: 10.1039/B512012H
Abstract: The gas-phase fragmentation reactions of a series of site-directed mutagenesis products of Staphylococcus aureus dihydroneopterin aldolase have been examined by multistage tandem mass spectrometry (MS/MS and MS(3)) in a linear quadrupole ion trap in order to explore the utility of this instrumentation for routine 'top-down' recombinant protein characterization. Following a rapid low resolution survey of the fragmentation behavior of the precursor ions from the wild type (WT) protein, selected charge states were subjected to detailed structural characterization by using high resolution 'zoom' and 'ultrazoom' resonance ejection MS/MS product ion scans. Dissociation of the [M + 18H](18+) charge state yielded a range of product ions from which extensive sequence information could be derived. In contrast, dissociation of the [M + 20H](20+) charge state resulted in a single dominant y(96) product ion formed by fragmentation between adjacent Ile/Gly residues, with only limited sequence coverage. Further extensive sequence information was readily obtained however, by MS(3) dissociation of this initial product. From the combined MS/MS and MS(3) spectra an overall sequence coverage of 66.9%, with fragmentation of 85 of the 127 amide bonds within the WT protein, was obtained. MS/MS and MS(3) of three of the four site-directed mutagenesis products (E29A), (Y61F) and (E81A) were found to yield essentially identical product ion spectra to the WT protein, indicating that these modifications had no significant influence on the fragmentation behavior. The specific site of modification could be unambiguously determined in each case by characterization of product ions resulting from fragmentation of amide bonds on either side of the mutation site. In contrast, MS/MS and MS(3) of the K107A mutant led to significantly different product ion spectra dominated by cleavages occurring N-terminal to proline, which restricted the ability to localize the modification site to within only an 8 amino acid region of the sequence. This work highlights the need for further studies to characterize the charge state, sequence and structural dependence to the low energy collision induced dissociation reactions of multiply protonated intact protein ions.
Publisher: American Chemical Society (ACS)
Date: 09-2007
DOI: 10.1016/J.JASMS.2007.06.014
Abstract: Mechanisms for the gas-phase fragmentation reactions of singly and multiply protonated precursor ions of the model S-alkyl cysteine sulfoxide-containing peptides GAILCGAILK, GAILCGAILR, and VTMGHFCNFGK prepared by reaction with iodomethane, iodoacetamide, iodoacetic acid, acrylamide, or 4-vinylpyridine, followed by oxidation with hydrogen peroxide, as well as peptides obtained from an S-carboxyamidomethylated and oxidized tryptic digest of bovine serum albumin, have been examined using multistage tandem mass spectrometry, hydrogen/deuterium exchange and molecular orbital calculations (at the B3LYP/6-31 + G(d,p) level of theory). Consistent with previous reports, CID-MS/MS of the S-alkyl cysteine sulfoxide-containing peptide ions resulted in the dominant "non-sequence" neutral loss of an alkyl sulfenic acid (XSOH) from the modified cysteine side chains under conditions of low proton mobility, irrespective of the alkylating reagent employed. Dissociation of uniformly deuterated precursor ions of these model peptides determined that the loss of alkyl sulfenic acid in each case occurred via a "charge-remote" five-centered cis-1,2 elimination reaction to yield a dehydroalanine-containing product ion. Similarly, the charge state dependence to the mechanisms and product ion structures for the losses of CO(2), CO(2) + H(2)O and CO(2) + CH(2)O from S-carboxymethyl cysteine sulfoxide-containing peptides, and for the losses of CH(2)CHCONH(2) and CH(2)CHC(5)H(4)N, respectively, from S-amidoethyl and S-pyridylethyl cysteine sulfoxide-containing peptide ions have also been determined. The results from these studies indicate that both the proton mobility of the peptide precursor ion and the nature of the S-alkyl substituent have a significant influence on the abundances and charge states of the product ions resulting from the various competing fragmentation pathways.
Publisher: Royal Society of Chemistry (RSC)
Date: 2009
DOI: 10.1039/B906577F
Abstract: We describe herein the synthesis and application of a range of diazo-functionalized materials as platforms for the solid phase enrichment of phosphorylated peptides from protein digests. Diazo-functionalized solid phase resins are employed to bind covalently and specifically with the phosphate moiety of a peptide substrate, allowing for non-phosphorylated peptides to be efficiently removed by filtration. The technique described herein is compatible with enrichment of phospho-serine, threonine and tyrosine residues and was used to successfully enrich phosphorylated substrates from beta-casein and ovalbumin digests in low-picomolar quantities.
Publisher: Elsevier BV
Date: 06-2014
DOI: 10.1016/J.JAAPOS.2014.01.006
Abstract: Leber congenital amaurosis is a severe retinal dystrophy that causes blindness or severe visual impairment, usually before the age of 1 year. We present the case of a 13-year-old girl with Leber congenital amaurosis who developed an exudative vasculopathy. She was successfully treated with cryotherapy and argon green laser. To our knowledge, only 4 cases of this condition in patients with Leber congenital amaurosis have been reported previously. This phenotype may be related to c.2991+1655A>G (p.Cys998X) mutations in the CEP290 gene.
Publisher: Elsevier BV
Date: 08-2016
DOI: 10.1016/J.JAAPOS.2016.03.015
Abstract: Chronic infantile neurological cutaneous and articular (CINCA) syndrome is a rare autosomal dominant autoinflammatory disease. We report the cases of monozygotic twins with CINCA syndrome whose predominant ocular manifestation was inflammatory rod-cone retinal dystrophy. Atypically, there were significant differences between twins in phenotype severity, suggestive of epigenetic differences and/or involvement of environmental factors.
Publisher: American Chemical Society (ACS)
Date: 16-10-2003
DOI: 10.1021/PR034054U
Abstract: We have evaluated the effect of lysine guanidination in peptides and proteins on the dissociation of protonated ions in the gas phase. The dissociation of guanidinated model peptide ions compared to their unmodified forms showed behavior consistent with concepts of proton mobility as a major factor in determining favored fragmentation channels. Reduction of proton mobility associated with lysine guanidination was reflected by a relative increase in cleavages occurring C-terminal to aspartic acid residues as well as increases in small molecule losses. To evaluate the effect of guanidination on the dissociation behavior of whole protein ions, bovine ubiquitin was selected as a model. Essentially, all of the amide bond cleavages associated with the +10 charge state of fully guanidinated ubiquitin were observed to occur C-terminal to aspartic acid residues, unlike the dissociation behavior of the +10 ion of the unmodified protein, where competing cleavage N-terminal to proline and nonspecific amide bond cleavages were also observed. The +8 and lower charge states of the guanidinated protein showed prominent losses of small neutral molecules. This overall fragmentation behavior is consistent with current hypotheses regarding whole protein dissociation that consider proton mobility and intramolecular charge solvation as important factors in determining favored dissociation channels, and are also consistent with the fragmentation behaviors observed for the guanidinated model peptide ions. Further evaluation of the utility of condensed phase guanidination of whole proteins is necessary but the results described here confirm that guanidination can be an effective strategy for enhancing C-terminal aspartic acid cleavages. Gas phase dissociation exclusively at aspartic acid residues, especially for whole protein ions, could be useful in identifying and characterizing proteins via tandem mass spectrometry of whole protein ions.
Publisher: Royal Society of Chemistry (RSC)
Date: 2009
DOI: 10.1039/B908241G
Publisher: Informa UK Limited
Date: 12-2013
DOI: 10.2147/OPTH.S54973
Publisher: Springer Science and Business Media LLC
Date: 27-10-2007
Publisher: American Chemical Society (ACS)
Date: 11-2008
DOI: 10.1021/AC801625E
Abstract: Chemical cross-linking combined with proteolytic digestion and mass spectrometry (MS) is a promising approach to provide inter- and intramolecular distance constraints for the structural characterization of protein topologies and functional multiprotein complexes. Despite the relative straightforwardness of these methodologies, the identification and characterization of cross-linked proteins presents a significant analytical challenge, due to the complexity of the resultant peptide mixtures, as well as the array of inter-, intra-, or "dead-end"-cross-linked peptides that may be generated from a single cross-linking experiment. To address these issues, we describe here the synthesis, characterization, and initial evaluation of a novel "fixed charge" sulfonium ion-containing crosslinking reagent, S-methyl 5,5'-thiodipentanoylhydroxysuc-cinimide. The peptide products obtained by reaction with this reagent are all shown to fragment exclusively via facile cleavage of the C-S bond directly adjacent to the fixed charge during CID-MS/MS, resulting in the formation of characteristic product ions that enable the presence and type (i.e., inter, intra, or dead-end) of the cross-linked products to be readily determined, independently of the "proton mobility" of the precursor ion. Subsequent isolation and dissociation of these products by MS3 provides additional structural information required for identification of the peptide sequences involved in the cross-linking reactions, as well as for characterization of the specific site(s) at which cross-linking has occurred. The specificity of these gas-phase fragmentation reactions, as well as the solubility and stability of the cross-linking reagent under aqueous conditions, suggests that this strategy holds great promise for use in future studies aimed at the structural analysis of large proteins or multiprotein assemblies.
Publisher: S. Karger AG
Date: 10-11-2020
DOI: 10.1159/000509942
Abstract: b i Objective: /i /b To define the characteristics of solitary idiopathic choroiditis (SIC) in a consecutive series of patients and propose a nomenclature change to idiopathic scleroma. b i Materials and Methods: /i /b Electronic patient records were retrospectively interrogated to identify all patients diagnosed with SIC between 2002 and 2019 in a tertiary referral ophthalmic hospital in the United Kingdom. b i Results: /i /b Thirty-four eyes of 34 patients were found to have SIC. The mean age at diagnosis was 48 years (range 24–78) and 23 patients (68%) were female. All lesions were located posterior to the equator, most frequently in the inferotemporal quadrant (13 eyes, 38%). The lesions had a mean largest basal diameter of 1.2 ± 0.4 disc diameters (range 0.5–2) and their distance to the optic disc had a mean of 1.2 ± 0.9 disc diameters (range 0–3.3). All lesions were intrascleral on enhanced depth imaging optical coherence tomography, demonstrating a hypo-reflective zone within the sclera, with an underlying hyper-reflective zone in some cases. No lesion enlarged or developed features consistent with active inflammation after a median follow-up time of 0.9 years (range 0–16.8). b i Discussion/Conclusion: /i /b Optical coherence tomography shows SIC to be an intrascleral lesion. Furthermore, we found no evidence of any inflammatory component. A nomenclature change to idiopathic scleroma is appropriate to prevent unnecessary investigation.
Publisher: S. Karger AG
Date: 13-07-2017
DOI: 10.1159/000477960
Abstract: Granuloma faciale (GF) is a rare, inflammatory, cutaneous disorder of unknown aetiology. It presents clinically as one or several well-circumscribed violaceous papules, plaques, and nodules almost exclusively confined to the facial region. Rarely, extrafacial lesions can occur, most often on sun-exposed sites. We report a case of extrafacial GF in a 63-year-old male with indolent lymphoma, who presented with plaques involving the right preauricular region and left posterior axilla. The clinical and histopathological findings were consistent with GF. Our case highlights the importance of performing skin biopsies in patients with persistent erythematous plaques and nodules, particularly to exclude important malignant and granulomatous differential diagnoses.
Publisher: American Chemical Society (ACS)
Date: 19-09-2006
DOI: 10.1021/JA063455I
Abstract: Dihydroneopterin aldolase (DHNA) catalyzes the conversion of 7,8-dihydroneopterin (1) to 6-hydroxymethyl-7,8-dihydropterin (4) in the folate biosynthetic pathway. Substitution of a conserved tyrosine residue at the active site of DHNA by phenylalanine converts the enzyme to a cofactor-independent oxygenase, which generates mainly 7,8-dihydroxanthopterin (6) rather than 4. 6 is generated via the same enol intermediate as in the wild-type enzyme-catalyzed reaction, but this species undergoes an oxygenation reaction to form 6. The conserved tyrosine residue plays only a minor role in the formation of the enol reaction intermediate but a critical role in the protonation of the enol intermediate to form 4.
Publisher: Royal Society of Chemistry (RSC)
Date: 2006
DOI: 10.1039/B600451M
Publisher: American Chemical Society (ACS)
Date: 10-2007
DOI: 10.1021/JP073040Z
Abstract: The surface-induced dissociation (SID) of six model peptides containing either methionine sulfoxide or aspartic acid (GAILM(O)GAILR, GAILM(O)GAILK, GAILM(O)GAILA, GAILDGAILR, GAILDGAILK, and GAILDGAILA) have been studied using a specially configured Fourier transform ion-cyclotron resonance mass spectrometer (FT-ICR MS). In particular, we have investigated the energetics and dynamics associated with (i) preferential cleavage of the methionine sulfoxide side chain via the loss of CH3SOH (64 Da), and (ii) preferential cleavage of the amide bond C-terminal to aspartic acid. The role of proton mobility in these selective bond cleavage reactions was examined by changing the C-terminal residue of the peptide from arginine (nonmobile proton conditions) to lysine (partially mobile proton conditions) to alanine (mobile proton conditions). Time- and energy-resolved fragmentation efficiency curves (TFECs) reveal that selective cleavages due to the methionine sulfoxide and aspartic acid residues are characterized by slow fragmentation kinetics. RRKM modeling of the experimental data suggests that the slow kinetics is associated with large negative entropy effects and these may be due to the presence of rearrangements prior to fragmentation. It was found that the Arrhenius pre-exponential factor (A) for peptide fragmentations occurring via selective bond cleavages are 1-2 orders of magnitude lower than nonselective peptide fragmentation reactions, while the dissociation threshold (E0) is relatively invariant. This means that selective bond cleavage is kinetically disfavored compared to nonselective amide bond cleavage. It was also found that the energetics and dynamics for the preferential loss of CH3SOH from peptide ions containing methionine sulfoxide are very similar to selective C-terminal amide bond cleavage at the aspartic acid residue. These results suggest that while preferential cleavage can compete with amide bond cleavage energetically, dynamically, these processes are much slower compared to amide bond cleavage, explaining why these selective bond cleavages are not observed if fragmentation is performed under mobile proton conditions. This study further affirms that fragmentation of peptide ions in the gas phase are predominantly governed by entropic effects.
Publisher: American Chemical Society (ACS)
Date: 12-2006
DOI: 10.1016/J.JASMS.2006.07.013
Abstract: To enable the development of improved tandem mass spectrometry based methods for selective proteome analysis, the mechanisms, product ion structures, and other factors influencing the gas-phase fragmentation reactions of methionine side-chain derivatized "fixed-charge" phenacylsulfonium ion containing peptide ions have been examined. Dissociation of these peptide ions results in the exclusive characteristic loss of the derivatized side chain, thereby enabling their selective identification. The resultant product ion(s) are then subjected to further dissociation to obtain sequence information for subsequent protein identification. Molecular orbital calculations (at the B3LYP/6-31 + G (d,p) level of theory) performed on a simple peptide model, together with experimental evidence obtained by multistage dissociation of a regioselectively deuterated methionine derivatized sulfonium ion containing tryptic peptide, indicate that fragmentation of the fixed charge containing peptide ions occurs via SN2 reactions involving the N- and C-terminal amide bonds adjacent to the methionine side chain, resulting in the formation of stable cyclic five- and six-membered iminohydrofuran and oxazine product ions, respectively. These studies further indicate that the rings formed via these neighboring group reactions are stable to further dissociation by MS3. As a consequence, the formation of b- or y-type sequence ions are "skipped" at the site of cyclization. Despite this, complete sequence information is still obtained because of the presence of both cyclic products.
Publisher: Wiley
Date: 14-02-2022
DOI: 10.1111/CEO.14056
Publisher: Humana Press
Date: 2009
Publisher: SAGE Publications
Date: 04-2008
DOI: 10.1255/EJMS.931
Abstract: A strategy involving the fixed-charge sulfonium ion derivatization, stable isotope labeling, capillary high-performance liquid chromatography and automated data dependent neutral loss scan mode tandem mass spectrometry (MS/MS) and “pseudo multiple mass spectrometry (MS 3 )” product ion scans in a triple quadrupole mass spectrometer has been developed for the “targeted” gas-phase identification, characterization and quantitative analysis of low abundance methionine-containing peptides present within complex protein digests. Selective gas-phase “enrichment” and identification is performed via neutral loss scan mode MS/MS, by low energy collision-induced dissociation of the derivatized methionine side chain, resulting in the formation of a single characteristic product ion. Structural characterization of identified peptides is then achieved by automatically subjecting the characteristic neutral loss product ion to further dissociation by data dependent product ion scan mode pseudo MS 3 under higher collision energy conditions. Quantitative analysis is achieved by measurement of the abundances of characteristic product ions formed by sequential neutral loss scan mode MS/MS experiments from “light” ( 12 C) and “heavy” ( 13 C) stable isotope encoded fixed-charge derivatized peptides. In contrast to MS-based quantitative analysis strategies, the neutral loss scan mode MS/MS method employed here was able to achieve accurate quantification for in idual peptides at levels as low as 100fmol and at abundance ratios ranging from 0.1 to 10, present within a complex protein digest.
Publisher: American Chemical Society (ACS)
Date: 14-11-2008
DOI: 10.1021/AC801768S
Abstract: The development of strategies directed toward comprehensive analysis of the phosphoproteome have undoubtedly been facilitated by recent advances in the application of ion trap tandem mass spectrometry-based techniques for routine phosphopeptide identification. However, when multiple potential sites of phosphorylation exist within a phosphorylated peptide sequence, unambiguous characterization of the site of phosphorylation remains a significant challenge. Here, the gas-phase fragmentation reactions of a series of 33 synthetic phospho-serine, -threonine, and -tyrosine peptides containing multiple potential phosphorylation sites have been examined using collision induced dissociation (CID) and multistage tandem mass spectrometry (MS/MS and MS(3)) in a linear quadrupole ion trap. From this study, 15 of the peptides (45%) gave rise to product ions that were formed following initial transfer of a phosphate group from the phosphorylated residue to an unmodified hydroxyl-containing amino acid residue upon CID-MS/MS. The propensity for this rearrangement was found to be highly dependent on the precursor ion charge state and amino acid composition (i.e, proton mobility) of the peptide and was observed predominantly for peptides under "nonmobile" or "partially mobile" protonation conditions. The observation of these rearrangement reactions and/or the lack of product ions that provided definitive evidence for the correct site of phosphorylation, limited the ability to unambiguously assign the correct site of phosphorylation to only 12 of the 33 peptides (36%). Furthermore, the observation of competing fragmentation reactions for the neutral loss of 98 Da from these precursor ions (i.e., the loss of H(3)PO(4) versus the combined losses of HPO(3) and H(2)O) indicates that CID-MS(3) of [M + nH - 98](n+) ions may not be used for unambiguous phosphorylation site localization.
Publisher: BMJ
Date: 17-06-2014
DOI: 10.1136/BJOPHTHALMOL-2014-305030
Abstract: To describe the microbiological spectrum and antibiotic sensitivities of organisms causing culture-proven endophthalmitis in Queensland, Australia, and to compare results with similar studies from other parts of Australia and other countries. A retrospective, multicentre, non-comparative, consecutive case series. Public hospital microbiology records from culture-positive endophthalmitis cases were reviewed over 15 years from June 1998 to June 2013. Outcome measures were type of endophthalmitis, vitreous isolates cultured and antibiotic sensitivities. 205 cases of culture-proven endophthalmitis were identified with a total of 229 isolates cultured. The most common organisms isolated were Staphylococcus epidermidis in 23.1%, Coagulase-negative Staphylococcus in 12.7%, Streptococcus viridans group in 10.0%, Candida species in 6.1%, fungal mold species in 5.7%. For gram-positive organisms, sensitivities were vancomycin 100%, cephazolin 79% and penicillin 47%. For gram-negative organisms, sensitivities were ceftazidime 100%, amikacin 100%, ciprofloxacin 100% and gentamicin 95.5%. For fungal isolates, sensitivities were voriconazole 93%, ketoconazole 89%, caspofungin 70% and hotericin B 58%. The microbiological spectrum and antibiotic sensitivities of endophthalmitis cases in Queensland, Australia, is similar to the spectrum of organisms causing endophthalmitis in other parts of Australia, North America and Europe. Empirical intravitreal vancomycin, ceftazidime and voriconazole are the most appropriate empirical antibiotics for suspected infective endophthalmitis.
Publisher: American Chemical Society (ACS)
Date: 07-2005
DOI: 10.1016/J.JASMS.2005.03.015
Abstract: To enable the development of a tandem mass spectrometry (MS/MS) based methodology for selective protein identification and differential quantitative analysis, a novel derivatization strategy is proposed, based on the formation of a "fixed-charge" sulfonium ion on the side-chain of a methionine amino acid residue contained within a protein or peptide of interest. The gas-phase fragmentation behavior of these side chain fixed charge sulfonium ion containing peptides is observed to result in exclusive loss of the derivatized side chain and the formation of a single characteristic product ion, independently of charge state or amino acid composition. Thus, fixed charge containing peptide ions may be selectively identified from complex mixtures, for ex le, by selective neutral loss scan mode MS/MS methods. Further structural interrogation of identified peptide ions may be achieved by subjecting the characteristic MS/MS product ion to multistage MS/MS (MS3) in a quadrupole ion trap mass spectrometer, or by energy resolved "pseudo" MS3 in a triple quadrupole mass spectrometer. The general principles underlying this fixed charge derivatization approach are demonstrated here by MS/MS, MS3 and "pseudo" MS3 analysis of side chain fixed-charge sulfonium ion derivatives of peptides containing methionine formed by reaction with phenacylbromide. Incorporation of "light" and "heavy" isotopically encoded labels into the fixed-charge derivatives facilitates the application of this method to the quantitative analysis of differential protein expression, via measurement of the relative abundances of the neutral loss product ions generated by dissociation of the light and heavy labeled peptide ions. This approach, termed "selective extraction of labeled entities by charge derivatization and tandem mass spectrometry" (SELECT), thereby offers the potential for significantly improved sensitivity and selectivity for the identification and quantitative analysis of peptides or proteins containing selected structural features, without requirement for extensive fractionation or otherwise enrichment from a complex mixture prior to analysis.
Publisher: Bentham Science Publishers Ltd.
Date: 02-2009
DOI: 10.2174/138620709787315445
Abstract: Significant effort has been extended in recent years toward the development and application of 'targeted' approaches for the identification, characterization and quantitative analysis of post-translational or process-induced protein modifications, based on the multistage tandem mass spectrometry (MS/MS and MS(3)) fragmentation reactions of their proteolytically derived peptide ions. Although these approaches have been successfully employed to date, the development of an improved understanding of the mechanisms and other factors (e.g., proton mobility, peptide conformation, product ion structures, etc.) that influence the multistage fragmentation reactions of modified peptide ions would facilitate further advances in the field. In this review, the important role of such mechanistic studies for rationalizing the effect of post-translational (e.g., phosphoserine- and phosphothreonine-containing peptides) and process-induced (e.g., oxidative modifications of methionine- and S-alkyl cysteine-containing peptides) protein modifications on the multistage collision induced dissociation gas-phase fragmentation reactions of proteolytically derived peptide ions are highlighted. Furthermore, recent efforts toward the development of chemical derivatization strategies for controlling and directing the gas-phase fragmentation reactions of protonated peptides toward the formation of analytically useful fragmentation pathways will be discussed, as well as the use of alternative dissociation techniques including electron capture dissociation (ECD) and electron transfer dissociation (ETD).
Publisher: S. Karger AG
Date: 20-05-2022
DOI: 10.1159/000524822
Abstract: Stickler syndrome is one of the most common inherited causes of retinal detachment in childhood. We present the case of a 6-year-old boy with Stickler syndrome who developed a retinal detachment in his better seeing eye after prolonged tr oline use. We suggest that tr olining should be avoided in all patients at increased risk of retinal detachment, especially in Stickler syndrome, and in those with other risk factors including high myopia and previous retinal detachments.
Publisher: Wiley
Date: 11-12-2006
DOI: 10.1002/JMS.1150
Abstract: The effect of trialkylsulfonium versus quaternaryalkylammonium ions on the multistage gas-phase fragmentation reactions of side chain, fixed-charge, cysteine-containing peptides has been examined in a quadrupole linear ion trap. These tandem mass spectrometry experiments reveal that selective loss of dialkylsulfide from fixed-charge sulfonium ion derivatives is the dominant fragmentation pathway regardless of the degree of proton mobility, indicating that it is the most energetically favored fragmentation pathway. In contrast, the loss of trimethylamine from the side chain of fixed-charge ammonium-ion-containing cysteine derivatives appears to be less energetically favored, and as a result extensive charge-remote fragmentation is observed under low proton mobility conditions, while under conditions of high proton mobility, amide bond fragmentation reactions dominate. These findings are supported by molecular orbital calculations at the B3LYP/6-31 + G(d, p) level of theory, which showed that the neutral loss of dimethylsulfide is both thermodynamically and kinetically preferred over the loss of trimethylamine.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2014
Publisher: American Chemical Society (ACS)
Date: 20-06-2008
DOI: 10.1021/AC8006076
Publisher: Springer Science and Business Media LLC
Date: 06-04-2022
DOI: 10.1186/S40942-022-00377-1
Abstract: To determine patient and surgical factors associated with the use of 360-degree laser retinopexy during primary pars plana vitrectomy (PPV) ± scleral buckle (SB) for rhegmatogenous retinal detachment (RRD) and its impact on surgical outcomes. Patients who underwent PPV ± SB for repair of non-complex RRD at a single centre were included in this retrospective study. The primary outcome was single surgery anatomical success (SSAS). Secondary outcomes included visual acuity, epiretinal membrane formation, the presence of cystoid macular oedema, tonic pupil and corneal epithelial defects. Multiple logistic regression and multivariate regression was used. The study included 192 cases, of which 130 received 360-degree laser. Worse preoperative logMAR visual acuity (P = 0.009), male sex (P = 0.060), higher PVR grades, supplemental SB (P = 0.0468) and silicone oil/C 3 F 8 t onade (P 0.0001) were associated with 360-degree laser use. No significant associations between 360-degree laser and SSAS (P = 0.079), final logMAR visual acuity (P = 0.0623), ERM development (P = 0.8208), postoperative CMO (P = 0.5946), tonic pupil (P 0.9999) or corneal epithelial defects (P = N/A) were found. 360-degree laser retinopexy during primary PPV ± SB for RRD was associated with more complex cases and more extensive operations. Even when accounting for this, there was no difference in surgical outcomes or complication rates.
Publisher: American Chemical Society (ACS)
Date: 26-06-2008
DOI: 10.1021/AC702472J
Abstract: Matrix-assisted laser desorption/ionization plates coated with poly(2-hydroxyethyl methacrylate) (PHEMA) brushes that are derivatized with Fe(III)-nitrilotriacetate (NTA) complexes allow selective, efficient phosphopeptide enrichment prior to analysis by mass spectrometry (MS). Fe(III)-NTA-PHEMA brushes (60 nm thick) have a phosphopeptide binding capacity of 0.6 microg/cm(2) and exhibit phosphopeptide recoveries of over 70%, whereas much thinner polymer films containing Fe(III)-NTA afford a recovery of only 20%, and a monolayer of Fe(III)-NTA shows a recovery of just 10%. Recoveries are determined by comparing signals from enriched unlabeled phosphopeptides with those of their deuterium-labeled analogues that were added to the plate just prior to addition of matrix. Mass spectra of phosphopeptide-containing s les enriched using Fe(III)-NTA-PHEMA-modified plates also demonstrate higher recoveries or fewer interfering peaks than corresponding spectra obtained with enrichment using several commercially available Fe(III)-containing films and resins or metal oxide materials. When analyzing tryptic digests of beta-casein, the Fe(III)-NTA-PHEMA brushes allow detection of as little as 15 fmol of phosphopeptide. Moreover, with both ovalbumin and beta-casein digests, phosphopeptide signals dominate the mass spectra obtained using these modified plates.
Publisher: Garval Editorial Ltda.
Date: 09-2023
DOI: 10.56499/JPPRES23.1661_11.5.797
Abstract: Aims: To investigate the potential antimalarial plant belonging to the Artocarpus genus, Artocarpus sericicarpus, and isolate the antimalarial active compound from leaves extract. Methods: The isolation of the antimalarial compound was based on bioassay-guided isolation. The compound isolation was conducted by chromatography and identified using spectroscopic techniques, including 1H, 13C, and 2D NMR. The compound was tested for its antimalarial activity against Plasmodium falciparum and evaluated for cytotoxicity using several cell lines, including Huh7, HepG2, BHK-21, and Vero cells. In silico investigation of the compound against falcipain-2 protein was conducted as well. Results: Fractionation and purification of dichloromethane leaves extract led to the isolation of a dihydrochalcone compound identified as 1-(2,4-dihydroxyphenyl)-3-[4-hydroxy-3-(3-methylbut-2-en-1-yl)phenyl]propan-1-one. The dihydrochalcone compound exhibited antimalarial activity with an IC50 value of 34.80 µM. Cytotoxicity test revealed CC50 values of the compound were more than 20 µg/mL, and the selectivity indexes (SI) were 4.50, 5.52, 3.02, and 6.68 on Huh7, HepG2, BHK-21, and Vero cells, respectively. The CC50 and SI indicated the nontoxic criteria of the compound. In silico investigation showed that the compound could bind to the falcipain-2 active sites. Conclusions: The dihydrochalcone compound identified as 1-(2,4-dihydroxyphenyl)-3-[4-hydroxy-3-(3-methylbut-2-en-1-yl)phenyl]propan-1-one was isolated from Artocarpus sericicarpus leaves extract showed antimalarial activity and the ability to bind to the falcipain-2 active sites on in silico investigation.
No related grants have been discovered for Tom Moloney.