Alpha-helix mimetics designed to disrupt the Bcl-xL/Bak interaction

ORGN 738

Jessica M. Davis, jmdavis@mail.fairfield.edu1, Hang Yin, hang.yin@yale.edu2, Gui-In Lee2, Anh Truong2, and Andrew D. Hamilton, andrew.hamilton@yale.edu2. (1) Department of Chemistry, Fairfield University, 1073 North Benson Rd, Fairfield, CT 06824, (2) Department of Chemistry, Yale University, 420 Temple St., Rm 327, New Haven, CT 06511
Deregulation of the apoptotic pathway leads to autoimmune and degenerative disorders, as well as cancer. The Bcl-xL/Bak interaction is a key step in the regulation of apoptosis and is therefore a therapeutic target. The Val74, Leu78, Ile81, and Ile85 residues of the α-helical BH3 domain of Bak have been identified as essential residues for binding. These residues correspond to the i, i+4, i+7, and i+11 residues of the α-helix. Using a α-helix mimetic approach to mimic these key residues, our group has developed small molecule inhibitors of the Bcl-xL/Bak interaction. The evolution of the design of these mimetics, as well as their synthesis, will be presented.

 

Lipids, Nucleotides, Biosynthesis, and Mimetics
8:00 AM-12:00 PM, Thursday, 1 September 2005 Washington DC Convention Center -- 202B, Oral

Division of Organic Chemistry

The 230th ACS National Meeting, in Washington, DC, Aug 28-Sept 1, 2005