个人简介

Scott Taylor's research is highly interdisciplinary ranging from synthetic organic chemistry to medicinal chemistry and enzymology, to the development of new bionanomaterials. He develops new synthetic methodology and applies it to the synthesis of novel biomolecules and materials such as modified steroids, carbohydrates, amino acids, peptides, nucleosides, nucleotides and starch nanoparticles. Novel biomolecules are evaluated as antibiotics and enzyme inhibitors, while the biomaterials are evaluated for their potential industrial applications. Biological and medicinal chemistry Synthetic methodology Enzymology Bionanomaterials Chair, Mass spec users committee, 2014-present Awards committee, 2013-present NMR users committee, 2000-present 1991 Ph.D. Chemistry, University of Toronto, Toronto, ON 1986 B.Sc. Biochemistry, McGill University, Montreal, QC

研究领域

Scott Taylor’s research program is currently focussed on four key areas: (1) the synthesis and study of cyclic lipodepsipeptide antibiotics; (2) the development of novel phosphorylation chemistry and its application to the synthesis of inhibitors of cytidine triphosphate synthase, an anti-cancer and antiviral target; (3) the development of inhibitors of steroid sulfatase, a breast cancer target and, (4) the modification of starch nanoparticles which are evaluated for their ability to extract oil from oil sands and as novel wound dressings. A wide variety of techniques are employed such as nuclear magnetic resonance, fluorimetry, high-performance liquid chromatography, protein purification, spectrophotometry, mass spectrometry, differential scanning calorimetry and dynamic light scattering.

Research in the Taylor Group is interdisciplinary ranging from synthetic and medicinal chemistry to enzymology and bionanotechnology. Bionanotechnology Nanomedicine We are interested in a class of antibiotics that function by forming nanopores in bacterial cell membranes. These antibiotics are lipodepsipeptides which means that they consist of a lipid attached to a cyclic peptide core and contain an ester bond in the cyclic portion. DaptomycinDaptomycin, an antibiotic used for treating difficult infections caused by gram-positive bacteria, is an example of this type of antibiotic. We are using daptomycin as a model system to elucidate the mechanism by which these antibiotics form nanopores and to determine the structure of the nanopores. We are also engineering novel cyclic lipodepsipeptides that self-assemble to form nanopores in bacterial membranes. Our ultimate goal is to development novel antibiotics that are effective against bacteria that are resistant to current antibiotic therapies. Bionanomaterials This research effort focuses on developing new bionanomaterials via modification and characterization of starch-based nanoparticles. Our goal is to develop these nanoparticles to the point where they can be used as “green” alternatives to petroleum-based polymers such as SB and SA latex. We develop novel synthetic methodologies to modify the nanoparticles and use techniques such as nuclear magnetic resonance (NMR), infrared spectroscopy and dynamic light scattering to characterize the modified particles. Synthetic methodology A significant part our research effort is directed towards the development of new synthetic methodologies. We are specifically interested in developing new methods for preparing organosulfates, polyphosphorylated and fluorinated, compounds as these compounds play very important roles in biological processes and/or are useful as probes and inhibitors of medicinally significant enzymes. Peptide chemistry The acquisition of bacterial resistance to conventional antibiotics A54145represents a major threat to human health. We are developing methods for preparing libraries of lipodepsipeptide antibiotics such as daptomycin and A54145. Our goal is to prepare analogs of these compounds that exhibit improved activity with resistant strains, reduced toxicity profiles and enhanced activity in the presence of lung surfactants so that they can be used for treating lung infections. Carbohydrate chemistry Our efforts in carbohydrate chemistry focus upon: the preparation of sulfated oligosaccharides the modification of starch nanoparticles Sulfated carbohydrates play key roles in important biological processes such as blot clotting, cell adhesion, and cell-cell communication to name but a few. Despite their widespread occurrence, elucidating their Tetrasaccharide portion of SB1a one of the most important carbohydrate antigens associated with human hepatocellular carcinomabiological function has been challenging mainly because they are isolated as complex mixtures from natural sources, and the chemical synthesis of pure, well defined sulfated oligosaccharide fragments is extremely challenging. We are using new sulfate protecting group methodology developed in the Taylor Group to develop more concise routes to these compounds. Nucleoside and nucleotide chemistry Many anticancer and antiviral drugs are nucleoside analogs. We are An intermediate analog of the cytidine triphosphate synthase reactioninterested in developing novel approaches to the synthesis of nucleosides and nucleoside polyphosphates and their conjugates and then applying this methodology to the synthesis of compounds that can be used as inhibitors and probes of therapeutically significant enzymes. Medicinal chemistry/enzymology Many of the compounds we prepare are designed to be biophysical probes STS with inhibitor modelled into active siteand inhibitors of medicinally significant enzymes. For example, we have discovered a novel class of highly potent reversible inhibitors of steroid sulfatase (STS) a recognized target for treating steroid-dependent cancers such as prostate and breast cancer. These inhibitors are under evaluation for their therapeutic potential. These inhibitors are being refined and improved through further efforts in synthesis and kinetic evaluation. Molecular modeling is used to determine how our inhibitors interact with the target enzymes (example shown is the interaction of one of our inhibitors with STS). Other enzymes that we are developing inhibitors for are cytidine triphosphate synthase (anti-cancer and anti-viral target) and protein tyrosine phosphatase 1B (diabetes target).

近期论文

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Mohamady, S.; Taylor, S.D. Synthesis of nucleoside triphosphates from 2'-3'-protected nucleosides using trimetaphosphate. Org. Lett. 2016, 18, 580-583. Taylor, R.; Butt, K.; Scott. B.; Zhang, T.; Muraih, J. K.; Mintzer, E.; Duhamekl, J.; Taylor, S. D.; Palmer, M. Two succesive Ca+2-dependent transitions medite membrane binding and oligomerization of daptomycin and the related antibiotic A54145. Biochim. Biophys. Acta – Biomembranes, 2016, 1858, 1999-2005. Lohani, C. R.; Taylor, S. D. A fresh look at the Staudinger reaction on azido esters: Formation of 2H-1,2,3-triazol-4-ols from a-azido ester using trialkylphosphines. Org Lett. 2016, 18, 4412-4415. Lohani, C.R.; Taylor, R.; Palmer, M.; Taylor, S.D. Solid-phase total synthesis of daptomycin and analogs. Org Lett. 2015, 17, 748-751. Mostafa, Y.A.; Kralt, B.; Rao, P.P.; Taylor, S.D. A-ring substituted 17β-arylsulfonamides of 17β-aminoestra-1,3,5(10)-trien-3-ol as highly potent reversible inhibitors of steroid sulfatase. Bioorg Med Chem. 2015, 23, 5681-5692.