Design of alpha-helix mimetics to disrupt protein function

ORGN 474

Jessica M. Davis and Andrew D. Hamilton. Department of Chemistry, Yale University, 225 Prospect St, P.O. Box 208107, New Haven, CT 06520
Alpha-helices on protein surfaces often mediate protein-protein, protein-DNA, and protein-RNA interactions. Mimicking α-helices with small molecules has been proven to be an effective means to disrupt these interactions. Our work focuses on the synthesis of small molecule mimetics of α-helices designed to disrupt protein function. Based on success with a terphenyl scaffold, novel α-helix mimetics employing biphenyl, bipyridine, and piperazine-pyrimidine scaffolds have been designed to mimic the i, i+1, and i+4 residues of the inhibitory α-helix of Vav, a protein involved in the signaling pathways that control proliferation, cytoskeletal growth, and apoptosis in lymphoid cells. Progress towards the synthesis of these small proteomimetics will be presented.
 

Total Synthesis, Process R&D, Combinatorial, Bioorganic, Physical Organic Chemistry
8:00 PM-10:00 PM, Tuesday, August 24, 2004 Pennsylvania Convention Center -- Hall D, Poster

Sci-Mix
8:00 PM-10:00 PM, Monday, August 23, 2004 Pennsylvania Convention Center -- Hall D, Sci-Mix

Division of Organic Chemistry

The 228th ACS National Meeting, in Philadelphia, PA, August 22-26, 2004