Douglas A. Andres
Professor
B.S. University of Wisconsin, Madison
Ph.D. Purdue University
dandres@pop.uky.edu
859-257-6775

Research Interests  |  Selected References  |  PubMed

Design and evaluation of anti-cancer therapeutics.           

In an ongoing collaboration with Dr. Peter Spielmann (Univ. Kentucky), we are involved in drug discovery efforts to target the protein Ras for cancer treatment. Whereas normal Ras function is required for proper cell growth, deregulated activity is linked to uncontrolled cell proliferation. Indeed, Ras genes are the most commonly mutated oncogenes in human cancer, and their malfunction is a critical mechanism driving over half of all human cancers. Ras proteins must be attached to the cell membrane in order to function, and this attachment requires modification by an unusual lipid called a farnesyl isoprenoid. Although the basis for this requirement in Ras protein function is not yet completely understood, a recent exciting development is that the enzyme responsible for the attachment of this lipid, farnesyl transferase (FTase), has become the target for a novel class of potential anticancer chemotherapeutic agents called FTase inhibitors. The mechanism of action for these drugs has turned out to be unexpectedly complex. We are involved in the design of a series of novel FTase inhibitors, and are characterizing the basis for their tumor inhibitory properties.

Publications:

Chehade, K.A.H, Andres, D.A., Morimoto, M., and Spielmann, H.P. (2000) Synthesis and Transfer of Farnesyl             Pyrophosphate Analogs to Ras by Protein Farnesyltransferase.     J. Organic Chem. 65, 3027-33.

Micali, E, Chehade, K.A.H., Isaacs, R.J., Andres, D.A., and Spielmann, H.P. (2001) Protein farnesyltransferase       isoprenoid             substrate discrimination on isoprene double         bonds and branched methyl groups. Biochem. 40, 12254-12265.