Robert Fecik, Ph.D.
University of Iowa, 1994
University of Kansas, 1999
Postdoc, The Scripps Research Institute and The Skaggs Institute for Chemical Biology, 1999-2001
8-121 Weaver-Densford Hall
University of Minnesota
College of Pharmacy
Department of Medicinal Chemistry
8-123 Weaver-Densford Hall
308 Harvard St. SE
Minneapolis, MN 55455
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.
- Drug Discovery
- Natural Products
- Anticancer Agents
- Organic Synthesis
- Faculty of 1000 Biology, Pharmacology & Drug Discovery section
- 2010 - Professor of the Semester, 2013 Pharm.D. Class (Twin Cities)
- 2010 - Professor of the Semester, 2013 Pharm.D. Class (Duluth)
- 2009 - Professor of the Semester, 2011 Pharm.D. Class (Twin Cities)
- 2003 - New Investigator Award, American Association of Colleges of Pharmacy
- 2002 - Professor of the Semester, 2004 Pharm.D. Class
Leggans, E. K.; Akey, D. L.; Smith, J. L.; Fecik, R. A. A General Scheme for Synthesis of Substrate-based Polyketide Labels for Acyl Carrier Proteins. Bioorg. Med. Chem. Lett. 2010, 20, 5939–5942.
Balasubramanian, R.; Raghavan, B.; Begaye, A.; Sackett, D. L.; Fecik, R. A. Total Synthesis and Biological Evaluation of Tubulysin U, Tubulysin V, and their Analogues. J. Med. Chem. 2009, 52, 238–240.
Balasubramanian, R.; Raghavan, B.; Sackett, D. L.; Fecik, R. A. Tubulysin Analogs Incorporating Desmethyl and Dimethyl Tubuphenylalanine Derivatives. Bioorg. Med. Chem. Lett. 2008, 18, 2996–2999.
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.