Structure-activity study of the N-terminal histidine of GLP-1

CHED 1317

Laura W. Marinelli, marinell@carleton.edu1, Taylor N. Lenton, tlenton@wellesley.edu2, Kathryn A. Lipford, klipford@wellesley.edu2, and David R. Haines, DHaines@Wellesley.edu2. (1) Department of Chemistry, Carleton College, 300 North College St., Northfield, MN 55057, (2) Department of Chemistry, Wellesley College, 106 Central Street, Wellesley, MA 02481
The production and release of insulin by pancreatic &beta-cells is mediated by Glucagon-like Peptide 1 (GLP-1). Studies have determined that the N-terminal histidine on GLP-1 is crucial for binding to and activation of the receptor GLP-1R. Substitutions of N-heterocyclic analogs of histidine for the N-terminal histidine have allowed us to refine our understanding of the structural requirements for the GLP-1R activation. Based on previous studies, we have extended our selection of histidine analogs to include symmetric (1) and asymmetric triazolylalanine (2) and pyrrolylalanine (3). Synthetic details will be provided, as will a comparison of the biological activities of these analogs with previous histidine substitutions.

 

Undergraduate Research Poster Session: Medicinal
2:00 PM-4:00 PM, Monday, March 26, 2007 Hyatt Regency Chicago -- Riverside Center, Poster

Division of Chemical Education

The 233rd ACS National Meeting, Chicago, IL, March 25-29, 2007