David Berkowitz, Willa Cather Professor
Willa Cather Professor
University of Nebraska–Lincoln
810 Hamilton Hall
Lincoln, Nebraska 68588-0304
Dr. David Berkowitz is active at the interface of synthetic organic chemistry and enzymatic chemistry. Projects in the group include the synthesis and study of unnatural analogues of biological molecules that have been designed to display interesting properties. This includes (a) fluorinated phosphonates designed to act as stable phosphate surrogates or ‘teflon phosphates,’ (b) unnatural, alpha-branched amino acids designed to function as ‘Trojan horse inactivators’ for vitamin B-6 dependent enzymes, and (c) unnatural analogues of the lignan natural product (-)-podophyllotoxin, designed to probe its binding to tubulin. Synthetic methodology development becomes part and parcel of these endeavors.
The newest area of activity in the group is in catalyst development. In particular, we are attempting to address the need for efficient and information-rich screening methods to support combinatorial approaches to catalyst discovery and optimization. This has led to the development of a method that we term In Situ Enzymatic Screening (ISES) that exploits enzyme-based reporters enabling the experimentalist to rapidly rank catalysts, ideally, in terms of relative rate and stereoselectivity. The scope, limitations and application of this technology are currently under investigation.
- 2009: Plenary Speaker, Visions in Chemistry Symposium, Sanofi-Aventis (Bridgewater, NJ)
(one of five speakers chosen nationally – along with Jeff Bode, Bruce Lipshutz, John Wood and Robert Grubbs)
(2005 Nobel Laureat in Chem) See the web site for more details
- 2009: Invited Speaker, 19th ACS Division of Fluorine Chemistry, Winter Fluorine Conference (St. Petersburg, FL)
- 2008-09: Japan Society for the Promotion of Science (JSPS) Fellowship
- 2008: Organizer, ACS Division of Organic Chemistry Symposium on Advances in Combinatorial Catalysis and Screening, 236th National ACS Meeting, Aug. 17-21, 2008 (Philadelphia, PA)
- 2008: Award for Outstanding Contributions to Undergraduate Research – University of Nebraska–Lincoln
- 2006: Visiting Professor, Max Planck Institut für molekulare Physiologie, Dortmund, Germany.
- Kaushik Panigrahi, David L. Nelson and David B. Berkowitz. “Unleashing a ‘True’ pSer-Mimic in the Cell.” Chemistry and Biology, 2012, 19, 666-667. pdf
- Sandeep K. Ginotra, Jacob A. Friest and David B. Berkowitz. “Halocarbocyclization Entry into the Oxabicyclo[4.3.1]decyl Exomethylene--Lactone Cores of Linearifolin and Zaluzanin A: Exploiting Combinatorial Catalysis.” Organic Letters, 2012, 4, 968-971 pdf
- Jacob A. Friest, Sylvain Broussy, Woo Jin Chung, and David B. Berkowitz. “Combinatorial Catalysis Employing a Visible Enzymatic Beacon in Real Time: Synthetically Versatile (Pseudo)Halometalation/Carbocyclizations.” Angewandte Chemie, Int. Ed. 2011, 50, 8895-8899. pdf
- Gregory A. Applegate, Ross W. Cheloha, David L. Nelson, and David B. Berkowitz. "A New Dehydrogenase from Clostridium acetobutylicum for Asymmetric Synthesis: Dynamic Reductive Kinetic Resolution entry into the Taxotère side chain." Chem Comm 2011, 47, 2420-2422. Featured in: SYNFACTS 2011, 3, 333. pdf
- David B. Berkowitz, Sangeeta Dey, Kannan R. Karukurichi and Weijun Shen. "A Method for Measuring the Stereoselectivity and Relative Rate for Organic Chemical Reactions." U.S. Patent No. 7,767,388, issued August 3, 2010.
- Jacob A. Friest, Yukari Maezato, Sylvain Broussy, Paul Blum, and David B. Berkowitz. "Use of a Robust Dehydrogenase from an Archael Hyperthermophile in Asymmetric Catalysis - Dynamic Reductive Kinetic Resolution Entry into (S)-Profens." JACS 2010, 132, 5930-5931. pdf
- Featured in Chemical and Engineering News, 2010, 88 (16), 34- 35. Featured in SYNFACTS, 2010, 8, 861.
- Nicola J. Baxter, Matthew W. Bowler, Tooba Alizadeh, Matthew J. Cliff, Andrea M. Hounslow, Bin Wu, David B. Berkowitz, Nicholas H. Williams, G. Michael Blackburn, and Jonathan P. Waltho. "Atomic details of near-transition state conformers for enzyme phosphoryl transfer revealed by MgF3? rather than by phosphoranes." PNAS 2010, 107 (10) 4555-4560. Featured in Chemical and Engineering News, 2010, 88 (9), 35. pdf
- David B. Berkowitz ; Sylvain Broussy; Argiris Efstratiadis; Apostolos Klinakis; Matthias Szabolcs.Columbia University in the City of New York, USA; University of Nebraska). “Analogues of (-)-Picropodophyllin, Synthesis and Uses Thereof.” PCT Int. Appl. 2009, 114pp. CODEN: PIXXD2 WO 2009100349 A1 20090813
- Kaushik Panigrahi, MariJean Eggen, Jun-Ho Maeng, Quanrong Shen, David B. Berkowitz* “The a,a-Difluorinated Phosphonate L-pSer-Analogue: An Accessible Chemical Tool for Studying Kinase-Dependent Signal Transduction, in Vitro and In Living Cells.” Chemistry and Biology 2009, 16(9), 928-936.
- David B. Berkowitz,* Kannan R. Karukurichi, Roberto de la Salud-Bea, Gourhari Maiti, Jill M. McFadden and Michelle L. Morris “Stereoselective Synthesis of Quaternary, alpha-Vinyl Amino Acids and their alpha-(2’Z-Fluoro)vinyl Congeners – Promising Candidates for PLP Enzyme Inactivation.” ACS Symposium-In-Print 2009, 1009, 288-303.
- Broussy, Sylvain, Cheloha, Ross W., and Berkowitz, David B.. "Enantioselective, Ketoreductase-Based Entry into Pharmaceutical Building Blocks: Ethanol as Tunable Nicotinamide Reductant." Organic Letters 2009, 11(2), 305-308.
Postdoctoral and Researchers, Graduates
- Sangeeta Dey, Ph.D. 2007 – Postdoctoral Fellow – Princeton University
- Weijun Shen, Ph.D. 2007 – Postdoctoral Fellow – Scripps Research Institute
- Kannan Karukurichi, Ph.D. 2006 – Postdoctoral Fellow – Johns Hopkins University
- Roberto de la Salud-Bea, Ph.D. 2006 – Postdoctoral Fellow –University of Michigan
- Mohua Bose, (Ph.D. 2002-postdoctoral at Scripps Res. Inst.);
- Sungjo Choi, (Ph.D. 2001- postdoctoral at Texas A&M);
- Huijie Li, (M.S. 2001-GlaxoSmithKline);
- Esmort Chisowa, (M.S. 2001-Pfizer);
- Wan-Jin Jahng, (Ph.D. 2000-postdoctoral at Harvard);
- Jill McFadden, (Ph.D. 2000-NIH postdoctoral fellowship, Johns Hopkins)