ORCID Profile
0000-0003-1818-4971
Current Organisation
Simon Fraser University
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Publisher: American Chemical Society (ACS)
Date: 31-12-2009
DOI: 10.1021/NP8003529
Publisher: Springer Science and Business Media LLC
Date: 08-2016
DOI: 10.1038/NBT.3597
Publisher: American Chemical Society (ACS)
Date: 05-08-2015
Abstract: Bastimolide A (1), a polyhydroxy macrolide with a 40-membered ring, was isolated from a new genus of the tropical marine cyanobacterium Okeania hirsuta. This novel macrolide was defined by spectroscopy and chemical reactions to possess one 1,3-diol, one 1,3,5-triol, six 1,5-diols, and one tert-butyl group however, the relationships of these moieties to one another were obscured by a highly degenerate (1)H NMR spectrum. Its complete structure and absolute configuration were therefore unambiguously determined by X-ray diffraction analysis of the nona-p-nitrobenzoate derivative (1d). Pure bastimolide A (1) showed potent antimalarial activity against four resistant strains of Plasmodium falciparum with IC50 values between 80 and 270 nM, although with some toxicity to the control Vero cells (IC50 = 2.1 μM), and thus represents a potentially promising lead for antimalarial drug discovery. Moreover, rigorous establishment of its molecular arrangement gives fresh insight into the structures and biosynthesis of cyanobacterial polyhydroxymacrolides.
Publisher: American Chemical Society (ACS)
Date: 23-12-2009
DOI: 10.1021/NP900622M
Publisher: Springer Science and Business Media LLC
Date: 23-10-2013
DOI: 10.1038/JA.2013.99
Publisher: Wiley
Date: 18-10-2011
Abstract: The total synthesis and stereochemical assignment of gallinamide A, an antimalarial depsipeptide of cyanobacterial origin, is described. Synthesis of the four possible N-terminal diastereoisomers of gallinamide A (including the natural product symplostatin 4) was achieved using a ergent strategy from a common imide fragment. The natural product and corresponding diastereoisomers were synthesized in 30-33% overall yield in a longest linear sequence of 8 steps. Comparative NMR spectroscopic studies of the four synthetic diastereoisomers with the isolated natural product demonstrated that gallinamide A possesses a dimethylated L-isoleucyl residue at the N-terminus. As such, we have shown that gallinamide A is structurally and stereochemically identical to symplostatin 4. Gallinamide A and its N-terminal diastereoisomers were also shown to possess significant antimalarial activity with IC(50) values in the nanomolar range against the 3D7 strain of Plasmodium falciparum.
Publisher: American Chemical Society (ACS)
Date: 16-03-2022
Publisher: Royal Society of Chemistry (RSC)
Date: 2019
DOI: 10.1039/C8NP90041H
Abstract: Correction for ‘The value of universally available raw NMR data for transparency, reproducibility, and integrity in natural product research’ by James B. McAlpine et al. , Nat. Prod. Rep. , 2018, DOI: 10.1039/c7np00064b.
Publisher: American Chemical Society (ACS)
Date: 18-05-2016
DOI: 10.1021/ACS.ORGLETT.6B01324
Abstract: The first total synthesis of the cyclic depsipeptide natural product teixobactin is described. Synthesis was achieved by solid-phase peptide synthesis, incorporating the unusual l-allo-enduracididine as a suitably protected synthetic cassette and employing a key on-resin esterification and solution-phase macrolactamization. The synthetic natural product was shown to possess potent antibacterial activity against a range of Gram-positive pathogenic bacteria, including a virulent strain of Mycobacterium tuberculosis and methicillin-resistant Staphylococcus aureus (MRSA).
Publisher: Springer Science and Business Media LLC
Date: 03-2017
DOI: 10.1038/NCOMMS14414
Abstract: Tuberculosis (TB) is responsible for enormous global morbidity and mortality, and current treatment regimens rely on the use of drugs that have been in use for more than 40 years. Owing to widespread resistance to these therapies, new drugs are desperately needed to control the TB disease burden. Herein, we describe the rapid synthesis of analogues of the sansanmycin uridylpeptide natural products that represent promising new TB drug leads. The compounds exhibit potent and selective inhibition of Mycobacterium tuberculosis , the etiological agent of TB, both in vitro and intracellularly. The natural product analogues are nanomolar inhibitors of Mtb phospho-MurNAc-pentapeptide translocase, the enzyme responsible for the synthesis of lipid I in mycobacteria. This work lays the foundation for the development of uridylpeptide natural product analogues as new TB drug candidates that operate through the inhibition of peptidoglycan biosynthesis.
Publisher: Royal Society of Chemistry (RSC)
Date: 2019
DOI: 10.1039/C7NP00064B
Abstract: With contributions from the global natural product (NP) research community, and continuing the Raw Data Initiative, this review collects a comprehensive demonstration of the immense scientific value of disseminating raw nuclear magnetic resonance (NMR) data, independently of, and in parallel with, classical publishing outlets.
Publisher: SAGE Publications
Date: 12-2018
Abstract: WITH THE INCREASE IN prevalence of food allergy (FA) in young children, early childhood education and care (ECEC) providers are likely to have more enrolments of children who are at risk of anaphylaxis. This study examines the status of FA management in ECEC, and assesses the services’ current readiness to prevent and manage FA. A cross-sectional study comprising an online survey with multiple-choice and open-ended questions was conducted with 53 long day care services in Western Australia. Among the respondents, 83 per cent of services had at least one child enrolled with FA, 96 per cent had an FA policy, and 91 per cent required staff to undertake anaphylaxis training. A high level of self-reported confidence and skills were demonstrated however, gaps were identified in risk-minimisation knowledge, use of adrenaline (epinephrine) autoinjectors and available resources. Extensive promotion of available resources will help improve compliance with anaphylaxis guidelines.
Publisher: American Chemical Society (ACS)
Date: 27-05-2010
DOI: 10.1021/JM100265S
Publisher: American Chemical Society (ACS)
Date: 25-05-2018
Abstract: Herein, we report our synthetic studies toward the skyllamycins, a highly modified class of nonribosomal peptide natural products which contain a number of interesting structural features, including the extremely rare α-OH-glycine residue. Before embarking on the synthesis of the natural products, we prepared four structurally simpler analogues. Access to both the analogues and the natural products first required the synthesis of a number of nonproteinogenic amino acids, including three β-OH amino acids that were accessed from the convenient chiral precursor Garner's aldehyde. Following the preparation of the suitably protected nonproteinogenic amino acids, the skyllamycin analogues were assembled using a solid-phase synthetic route followed by a final stage solution-phase cyclization reaction. To access the natural products (skyllamycins A-C) the synthetic route used for the analogues was modified. Specifically, linear peptide precursors containing a C-terminal amide were synthesized via solid-phase peptide synthesis. After cleavage from the resin the N-terminal serine residue was oxidatively cleaved to a glyoxyamide moiety. The target natural products, skyllamycins A-C, were successfully prepared via a final step cyclization with concomitant formation of the unusual α-OH-glycine residue. Purification and spectroscopic comparison to the authentic isolated material confirmed the identity of the synthetic natural products.
Publisher: Oxford University Press (OUP)
Date: 18-11-2022
DOI: 10.1093/NAR/GKAC1049
Abstract: With an ever-increasing amount of (meta)genomic data being deposited in sequence databases, (meta)genome mining for natural product biosynthetic pathways occupies a critical role in the discovery of novel pharmaceutical drugs, crop protection agents and biomaterials. The genes that encode these pathways are often organised into biosynthetic gene clusters (BGCs). In 2015, we defined the Minimum Information about a Biosynthetic Gene cluster (MIBiG): a standardised data format that describes the minimally required information to uniquely characterise a BGC. We simultaneously constructed an accompanying online database of BGCs, which has since been widely used by the community as a reference dataset for BGCs and was expanded to 2021 entries in 2019 (MIBiG 2.0). Here, we describe MIBiG 3.0, a database update comprising large-scale validation and re-annotation of existing entries and 661 new entries. Particular attention was paid to the annotation of compound structures and biological activities, as well as protein domain selectivities. Together, these new features keep the database up-to-date, and will provide new opportunities for the scientific community to use its freely available data, e.g. for the training of new machine learning models to predict sequence-structure-function relationships for erse natural products. MIBiG 3.0 is accessible online at
Publisher: American Chemical Society (ACS)
Date: 30-11-2021
DOI: 10.1021/ACS.JMEDCHEM.1C01407
Abstract: Herein, we report the design and synthesis of inhibitors of
Publisher: Wiley
Date: 11-10-2017
Abstract: The skyllamycins are a family of highly functionalized non-ribosomal cyclic depsipeptide natural products which contain the extremely rare α-OH-glycine functionality. Herein the first total synthesis of skyllamycins A-C is reported, together with the biofilm inhibitory activity of the natural products. Linear peptide precursors for each natural product were prepared through an efficient solid-phase route incorporating a number of synthetic modified amino acids. A novel macrocyclization step between a C-terminal amide and an N-terminal glyoxylamide moiety served as a key transformation to install the unique α-OH-glycine unit and generate the natural products in the final step of the synthesis.
Location: United States of America
No related grants have been discovered for Roger Linington.