Design and synthesis of PPII mimics as substrate probes of the active site occupancy requirements of cGMP-dependent protein kinase

ORGN 935

Rakesh R. Ganorkar, rganorka@uvm.edu1, Shivkumar Raidas2, Amarnath Natarajan, anataraj@zoo.uvm.edu1, Wolfgang Dostmann2, and José S. Madalengoitia, jmadalen@zoo.uvm.edu1. (1) Department of Chemistry, University of Vermont, 82 University Place, Burlington, VT 05405, (2) Department of Pharmacology, University of Vermont, Burlington, VT 05405
Although the primary structures recognized by protein kinases have been the focus of extensive studies, the conformation in which peptide substrates bind to protein kinase active sites is a problem that has not been extensively explored. This works describes a proposal that cGMP dependent protein kinase (PKG) binds peptides substrates in its active site in the poly-L-proline type II (PPII) conformation. The design and synthesis of PPII mimics will be described. In addition, the evaluation of PPII mimics as PKG substrates that map the conformational active site occupancy requirements of PKG will be presented.
 

Proteins, Peptides, Amino Acids, and Enzyme Inhibitors
1:00 PM-5:00 PM, Thursday, 14 September 2006 Moscone Center -- Room 131, Oral

Division of Organic Chemistry

The 232nd ACS National Meeting, San Francisco, CA, September 10-14, 2006