Priestley, Nigel - University of Montana - Department of Chemistry and Biochemistry

个人简介

Nigel Priestley came to the University of Montana in 1999 from the Ohio State University. He earned his Ph.D. from The University of Southampton, UK in 1991. While at Ohio State University he was an Assistant Professor in the Division of Medicinal Chemistry and Pharmacognosy.

研究领域

Our group interests are firmly rooted in natural product chemistry, biochemistry, and biosynthesis. The unifying theme of our researchis to gain an understanding of how natural products are made so that the organisms that produce them can be manipulated to produce 'non-natural' natural products. Nonactin is a macrocyclic polyether ionophore antibiotic. The structure is a tetramer composed of two monomers of(+)-nonactic acid and two monomers of (-)-nonactic acid. We are currently making new analogs of nonactin by genetic engineering of the nonactin biosynthesis gene cluster and through the use of recombinant, overexpressed biosynthesis enzymes in a synergistic approach with synthetic organic chemistry. The work also encompasses the synthesis and use of stable isotope labeled precursors to elucidate the mechanism of the reactions catalyzed by the nonactate poyketide synthase. The anthracycline compounds daunorubicin and doxorubicin are significant anti-cancer chemotherapeutics. We are studying the details of their biosynthesis which includes the chemistry catalyzed by the type II anthracycline PKS and the post-PKS modifications. Two emphases of the research are the enzymes DoxA (P450 monooxygenase) and DnmS (a glycosyl transferase) which are important enzymes catalyzing post-PKS processing steps. Other research includes the cloning and analysis of the biosynthesis gene clusters responsible for making a number of other polyketide metabolites and the use of combinatorial methods for producing large libraries of complex, stereo-rich, potential lead structures based upon natural product scaffolds. More information on the individual research projects can be found on the personal web pages.

近期论文

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Phillips, Joshua B.; Smith, Adrienne E.; Kusche, Brian R.; Bessette, Bradley A.; Swain, P. Whitney III; Bergmeier, Stephen C.; McMills, Mark C.; Wright, Dennis L. and Priestley, Nigel D. Bioorg. Med. Chem. Letts., 2010, 20(19), 5936 – 5938 "Natural product derivatives with bactericidal activity against Gram-positive pathogens including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecalis." Kusche, Brian R.; Smith, Adrienne E.; McGuirl, Michele A.; Priestley, Nigel D. Journal of the American Chemical Society, 2009, 131(47), 17155 – 17165 "Alternating pattern of stereochemistry in the nonactin macrocycle is required for antibacterial activity and efficient ion binding." Paulsen, Janet L.; Liu, Jieling; Bolstad, David B.; Smith, Adrienne E.; Priestley, Nigel D.; Wright, Dennis L. and Anderson, Amy C. Bioorg. Med. Chem., 2009, 17(14), 4866 – 4872 "In vitro biological activity and structural analysis of 2,4-diamino-5-(2'-arylpropargyl)pyrimidine inhibitors of Candida albicans." Kusche, Brian R.; Phillips, Joshua B. and Priestley, Nigel D. Bioorg. Med. Chem. Letts., 2009, 19(4), 1233-1235 "Nonactin biosynthesis: Setting limits on what can be achieved with precursor-directed biosynthesis." Liu, Jieling; Bolstad, David B.; Smith, Adrienne E.; Priestley, Nigel D.; Wright, Dennis L. and Anderson, Amy C. Chemical Biology and Drug Design, 2009, 73(1), 62 – 74 "Probing the active site of Candida glabrata dihydrofolate reductase with high resolution crystal structures and the synthesis of new inhibitors." Bierelein, Jennifer M.; Frey, Kathleen M.; Bolstad, David B.; Pelphrey, Phillip M.; Joska, Tammy M.; Smith, Adrienne E.; Priestley, Nigel D; Wright, Dennis L. and Anderson, Amy C. Journal of Medicinal Chemistry, 2008, 51(23), 7532 –7540 "Synthetic and crystallographic studies of a new inhibitor series targeting Bacillus anthracis dihydrofolate reductase." Liu, Jieling; Bolstad, David B.; Smith, Adrienne E.; Priestley, Nigel D.; Wright, Dennis L. and Anderson, Amy C. Chemistry and Biology, 2008, 15(9), 990 – 996 "Structure-guided development of efficacious antifungal agents targeting Candida glabrata dihydrofolate reductase." Luesse, Sarah L.; Wells, Gregg; Nayek, Abhijit; Smith, Adrienne E.; Kusche, Brian R.; Bergmeier, Stephen C.; McMills, Mark C.; Priestley, Nigel D. and Wright, Dennis L. Bioorg. Med. Chem. Letts., 2008, 18(14), 3946 – 3949 "Natural products in parallel synthesis: Triazole libraries of nonactic acid." Slade, Peter G., Priestley, Nigel D. and Sugden, Kent D. Organic Letters, 2007, 9(22), 4411 – 4414 "Spiriminohydantoin as an oxo-atom transfer product of 8-oxo-2'-deoxyguanosine oxidation by chromium(V)." Nikodinovic, Jasmina and Priestley, Nigel D. Plasmid, 2006, 56(3), 223 – 227 "A second generation snp-derived Escherichia coli-Streptomyces shuttle expression vector that is generally transferable by conjugation." Dinges, Jennifer M.; Bessette, Bradley A.; Cox, James E.; Redder, Casey R. and Priestley, Nigel D. Biotechnology progress, 2006, 22(5), 1354 – 1357 "Lipase-mediated purification of methyl nonactate, an important natural product building block for diversity-oriented synthesis." Nikodinovic, Jasmina; Dinges, Jennifer M.; Bergmeier, Stephen C.; McMills, Mark C.; Wright, Dennis L. and Priestley, Nigel D. Organic Letters, 2006, 8(3), 443 – 445 "Resolution of methyl nonactate by Rhodococcus erythropolis under aerobic and anaerobic conditions."