Robert A. Fecik
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Robert A. Fecik, Ph.D.
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Updated April 19, 2007
Education:
B.S., University of Iowa, Pharmacy, 1994
Ph.D., University of Kansas, Medicinal Chemistry, 1999
American Cancer Society Postdoctoral Fellow, The Scripps Research Institute and The Skaggs Institute for Chemical Biology, Chemistry, 1999-2001
Research Interests:
Natural products continue to inspire the development of new methods for drug discovery and synthesis. The focus of my laboratory is on ways to combat antibiotic and anticancer multidrug resistance through the combinatorial biosynthesis and total synthesis of natural products. Macrolide and ketolide antibiotics are one of the most widely used classes of anti-infective agents. Pikromycin, a natural ketolide antibiotic, offers a unique structural scaffold for the discovery of new macrolides. Our laboratory studies the biosynthesis of pikromycin in Streptomyces venezuelae, and has synthesized numerous late stage biosynthetic intermediates to examine the mechanisms of pikromycin biosynthesis. We have also synthesized polyketide-based affinity labels as a new approach to obtain structural and mechanistic information about key enzymes for pikromycin biosynthesis and other polyketide natural products. The tubulysins are a potent new class of tubulin polymerization inhibitors effective against multidrug-resistant cancer cell lines. Our laboratory has developed a route to these natural products by total synthesis that is amenable to the synthesis of the tubulysins and analogs for the potential treatment of cancers.
News:
Our total synthesis of narbonolide and pikromycin (J. Org. Chem. 2006, 71, 9853–9856) was recently featured in the Totally Synthetic blog.
Robert will be Co-Chair of a symposium on fatty acid synthase inhibitors with Kevin Reynolds at the ACS National Meeting in New Orleans on April 10, 2008.
Robert was recently invited to be a member of the Pharmacology & Drug Discovery section of the Faculty of 1000 Biology. Click here to view the list of Faculty of 1000 Biology members.
Two of our papers were published in Nature Chemical Biology describing the first crystal structures of a modular polyketide synthase domain with substrate mimics bound in the active site have garnered press in major scientific, TV, newspaper, business, and online media outlets:
Nature Chemical Biology News & Views
KARE 11 TV (Minneaoplis NBC affiliate), with video
St. Paul Pioneer Press
University of Minnesota press release
Upcoming Seminars and Meetings:
March 16 San Diego State University, Department of Chemistry & Biochemistry
March 25–29 American Chemical Society 233rd Annual Meeting
April 13–15 MIKI Meeting
June 10–15 Gordon Research Conference, Bioorganic Chemistry
Select Publications:
Venkatraman, L.; Salomon, C. E.; Sherman, D. H.; Fecik, R. A. Total Synthesis of Narbonolide and Biotransformation to Pikromycin. J. Org. Chem. 2006, 71, 9853–9856.
Akey, D. L.; Kittendorf, J. D.; Giraldes, J. W.; Fecik, R. A.; Sherman, D. H.; Smith, J. L. Structural Basis for Macrolactonization by the Pikromycin Thioesterase. Nat. Chem. Biol. 2006, 2, 537–542.
Giraldes, J. W.; Akey, D. L.; Kittendorf, J. D.; Sherman, D. H.; Smith, J. L.; Fecik, R. A. Structural and Mechanistic Insights of Polyketide Macrolactonization from Polyketide-based Affinity Labels. Nat. Chem. Biol. 2006, 2, 531–536.
Venkatraman, L.; Aldrich, C. C.; Sherman, D. H.; Fecik, R. A. Formal Total Synthesis of the Polyketide-derived Macrolactone Narbonolide. J. Org. Chem. 2005, 70, 7267–7272.
Aldrich, C. C.; Venkatraman, L.; Sherman, D. H; Fecik, R. A. Chemoenzymatic Synthesis of the Polyketide Macrolactone 10-Deoxymethynolide. J. Am. Chem. Soc. 2005, 127, 8910–8911.
Aldrich, C. C.; Beck, B. J.; Fecik, R. A.; Sherman, D. H. Biochemical Investigation of Pikromycin Biosynthesis Employing Native Penta- and Hexaketide Chain Elongation Intermediates. J. Am. Chem. Soc. 2005, 127, 8441–8452.