Rational Design of Regulators of Programmed Cell Death in Human Breast Cancer
Annual rept. 1 Jul 1999-30 Jun 2000
ROCKEFELLER UNIV NEW YORK
Pagination or Media Count:
The purpose of this research is to develop a better understanding of the intricate pathways of cell death and their contributions to breast cancers, with the goal of designing potential therapeutic agents for inducing or regulating apoptotic processes in breast cancer. The scope of this research has included the determination by NMR of the structure of the first proapoptotic BCL-2 like molecule BID and its analysis, identifying key structural issues associated with a the caspase catalyzed cleavage of part of BID to produce a truncated form, tBID, and b a likely structural model for the necessity of exposure of portion of one helix of BID and other homologues, in the BM3 motif. Current work focuses on efficient expression of the large quantities of BCL-2 family members for structural and biochemical assay, design and synthesis of BH3 mimics, and preliminary characterization of tBID in membrane bound form, prior to attempts to identify complexes of tBID for structural analysis. These studies have elucidated the structural basis for a set of molecular interactions that regulate programmed cell death, and allow the design of novel interventional agents that have investigative and therapeutic potential.
- Anatomy and Physiology
- Medicine and Medical Research