Altering the selectivity of high affinity BH3 peptides for antiapoptotic BH proteins

BIOL 16

Melissa D. Boersma, mboersma@wisc.edu1, Erik B. Hadley1, York Tomita2, and Samuel H Gellman1. (1) Department of Chemistry, University of Wisconsin-Madison, 1101 University Ave, Madison, WI 53706, (2) Lombardi Cancer Center, Georgetown University
Bcl-2 homology (BH) proteins regulate programmed cell death by affecting mitochondrial membrane integrity and initiating the caspase cascade. The protein-protein interactions among the BH family members are tightly interwoven, and the mechanism of this regulation is not fully understood. Short peptides derived from a subclass of the BH proteins (BH3 only) have been shown to initiate apoptosis. Here we report structure activity relationships among a family of peptides derived from a BH3 peptide that is known to bind promiscuously to anti-apoptotic BH proteins. Our results were obtained via parallel peptide synthesis and screening. The insights gained from this study allowed us to identify new peptides that are selective for different anti-apoptotic BH proteins, via relatively simple modifications of the original promiscuous sequence.
 

Frontiers in Chemical Biology
5:00 PM-7:00 PM, Sunday, August 19, 2007 BCEC -- Exhibit Hall - B2, Poster

Division of Biological Chemistry

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007