Faculty

Dale DrueckhammerDale G. Drueckhammer, Professor

B.S. Tarleton State University, 1983
Ph.D. Texas A and M University, 1987
NIH Postdoctoral Fellowship, Harvard Medical School, 1987-1989
Alfred P. Sloan Foundation Fellowship, 1995-1997

741 Chemistry
Phone: (631) 632-7923
Email:

Bioorganic Chemistry

My research can be summarized as the design, synthesis, and study of new organic molecules, primarily directed toward biological applications. The majority of work in my group involves the design and synthesis of artificial receptors for biological compounds and ions. Current specific targets for receptor design include glucose, sialic acid, neurotransmitters, nucleic acids, and metal ions. The design aspects of this work involve extensive use of computer modeling and novel use of the computer program CAVEAT. CAVEAT is used to discover structures that allow precise positioning of functional groups for efficient multivalent interaction with the target compound. Compounds designed using our computer-based methods are synthesized and studied as receptors for the targeted biological compounds and ions in solution. Incorporation of fluorescent signaling moieties into these receptors provides fluorescence-based sensors of potential use in medical and environmental diagnostic applications. We have recently completed the synthesis of a fluorescent receptor/sensor for glucose, which is of interest for potential application as a glucose sensor for persons with diabetes. We are now extending this project to the development of simple biomimetic catalysts, using CAVEAT to discover backbone structures for precise relative positioning of catalytic groups.

We are also continuing to pursue an older project in my group directed at the chemistry and enzymology of Coenzyme A (CoA). My group has developed a versatile method for the synthesis of analogs of CoA using a combination of enzymatic and nonenzymatic reactions. This method is being used to prepare CoA analogs that mimic the transition states and intermediates in enzyme-catalyzed reactions. These analogs are used to probe mechanistic and structural questions in CoA utilizing enzymes. As about 4% of all enzymes use CoA or a thioester of CoA as a substrate, this work can be applied to a large number of enzymes, including enzymes of pharmaceutical importance. One such target is the protein palmitoyltransferase, which catalyzes transfer of the palmitoyl group from palmitoyl-CoA to a cysteine thiol group of a peptide or protein. Analogs of palmitoyl-CoA are being prepared to inhibit this reaction. These analogs will be useful in studying for example the palmitoylation of the ras protein, implicated in about 30% of all cancers.

All of the research in my group is based largely on synthesis and students in my group spend most of their time doing synthetic chemistry. Individual projects may also involve computational modeling and measurements of binding constants by NMR, calorimetry, fluorescence, etc. The CoA project involves a variety of biochemical techniques including enzyme isolation and assays of enzyme activity.

Awards/Honors

  • EPA Green Chemistry Challenge Award, 2000.

Publications

Chemistry of CoA-Dependent Enzymes, D. G. Drueckhammer, Wiley Encyclopedia of Chemical Biology. DOI: 10.1002/9780470048672.wecb093, Online Posting Date: March 14, 2008.

Quantifying Intrinsic Specificity: A Potential Complement to Affinity in Drug Screening, J. Wang, X. Zheng, Y. Yang, D. G. Drueckhammer, W. Yang, G. Verkhivker, and E. Wang, Phys. Rev. Lett., 2007, 99, 198101.

Inhibition of Mammalian Target of Rapamycin Signaling by 2-(morpholin-1-yl)pyrimido[2,1-a]isoquinoin-4-one, L. M. Ballou, E. S. Selinger, J. Y. Choi, D. G. Drueckhammer, and R. Z. Lin, J. Biol. Chem., 2007, 282, 24463-24470.

Interaction of Halide and Carboxylate Ions with 4,5-Diacetamidoacridine-9(10H)-one: Thermodynamics of Association and Deprotonation Events, C. Lin, V. Simov, and D. G. Drueckhammer, J. Org. Chem., 2007, 72, 1742-1746.

Computer-guided design of a Cu(II) receptor and sensor, C. Lin and D. G. Drueckhammer, New. J. Chem., 2006, 30, 1725-1730.

A Modular Molecular Tweezer Designed using CAVEAT, H. Huang and D. G. Drueckhammer, Chem. Commun., 2006, 2995-2997.

Virtual Hydrocarbon and Combinatorial Databases for Use with CAVEAT, Y. Yang, D. Nesterenko, R. P. Trump, K. Yamaguchi, P. A. Bartlett, and D. G. Drueckhammer, J. Chem. Information Modelling, 2005, 45, 1820-1823.

A Computer-Designed Macrocyclic Zinc Receptor, H. Huang and D. G. Drueckhammer, Chem. Commun., 2005, 5196-5198.

Transition State Modeling and Catalyst Design for Hydrogen Bond-Stabilized Enolate Formation, Y. Zhu and D. G. Drueckhammer, J. Org. Chem., 2005, 70, 7755-7760.

The Importance of the Amide Bond Nearest the Thiol Group in Enzymatic Reactions of Coenzyme A, J. Xun, H. Huang, K. W. Vogel, D. G. Drueckhammer, Bioorganic Chem., 2005, 33, 90-107.

Computational Study of the Citrate Synthase Catalyzed Deprotonation of Acetyl-Coenzyme A and Fluoroacetyl-Coenzyme A: Demonstration of a Layered Quantum Mechanical Approach W. Yang and D. G. Drueckhammer, J. Phys. Chem. B, 2003, 107, 5986-5994.

Acyl group specificity at the active site of tetrahydrodipicolinate N-succinyltransferase, Beaman TW, Vogel KW, Drueckhammer DG, Blanchard JS, Roderick SL, PROTEIN SCIENCE 11 (4): 974-979 APR 2002

An efficient synthesis of geminal di-sulfones, Zhu YM, Drueckhammer DG, TETRAHEDRON LETTERS 43 (8): 1377-1379 FEB 18 2002

Understanding the relative acyl-transfer reactivity of oxoesters and thioesters: Computational analysis of transition state delocalization effects, Yang W, Drueckhammer DG, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 123 (44): 11004-11009 NOV 7 2001

Computer-guided design in molecular recognition: Design and synthesis of a glucopyranose receptor, Yang W, He H, Drueckhammer DG, ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 40 (9): 1714-1718 2001

Identification of yacE (coaE) as the structural gene for dephosphocoenzyme a kinase in Escherichia coli K-12, Mishra PK, Park PK, Drueckhammer DG, JOURNAL OF BACTERIOLOGY 183 (9): 2774-2778 MAY 2001

Development of a novel polynucleotide mimic, Liu Y, Drueckhammer DG, ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY 220: 244-ORGN Part 2 AUG 20 2000

Design and synthesis of a novel glucose receptor and sensor, Yang W, Drueckhammer DG ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY 220: 245-ORGN Part 2 AUG 20 2000

Computational studies of oxoester and thioester reactivity, Yang W, Drueckhammer DG ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY 220: 271-ORGN Part 2 AUG 20 2000

Fluoroketones and other analogs of acetyl-coenzyme A, Xun JJ, Drueckhammer DG ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY 220: 352-ORGN Part 2 AUG 20 2000

Recent advances in Coenzyme A analog synthesis, Mishra P, Drueckhammer DG, ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY 220: 353-ORGN Part 2 AUG 20 2000

Computational studies of the aminolysis of oxoesters and thioesters in aqueous solution Yang W, Drueckhammer DG, ORGANIC LETTERS 2 (26): 4133-4136 DEC 28 2000

Investigating the role of the geminal dimethyl groups of coenzyme A: Synthesis and studies of a didemethyl analogue, Vogel KW, Stark LM, Mishra PK, Yang W, Drueckhammer DG BIOORGANIC & MEDICINAL CHEMISTRY 8 (10): 2451-2460 OCT 2000

Coenzyme A analogues and derivatives: Synthesis and applications as mechanistic probes of coenzyme A ester-utilizing enzymes, Mishra PK, Drueckhammer DG, CHEMICAL REVIEWS 100 (9): 3283-3309 SEP 2000

Solid state NMR studies of hydrogen bonding in a citrate synthase inhibitor complex Gu ZT, Drueckhammer DG, Kurz L, Liu K, Martin DP, McDermott A, BIOCHEMISTRY 38 (25): 8022-8031 JUN 22 1999

Development of a second generation coenzyme A analogue synthon, Bibart RT, Vogel KW, Drueckhammer DG, JOURNAL OF ORGANIC CHEMISTRY 64 (8): 2903-2909 APR 16 1999

Novel cofactor derivatives and cofactor-based models, Mishra PK, Drueckhammer DGCURRENT OPINION IN CHEMICAL BIOLOGY 2 (6): 758-765 DEC 1998

Dynamic enzymatic resolution of thioesters, Um PJ, Drueckhammer DG, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 120 (23): 5605-5610 JUN 17 1998

A reversed thioester analogue of acetyl-coenzyme A: An inhibitor of thiolase and a synthon for other acyl-CoA analogues, Vogel KW, Drueckhammer DG, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 120 (14): 3275-3283 APR 15 1998

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