Determining the reactive properties of GLP-1

CHED 1290

Laura W. Marinelli, marinell@carleton.edu1, Kathryn A. Lipford, klipford@wellesley.edu2, Taylor N. Lenton, tlenton@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, 21 Wellesley College Rd #5023, Wellesley, MA 02481
Glucagon-like Peptide (GLP-1) initiates the production and release of insulin by pancreatic β-cells. The N-terminal histidine of GLP-1 is crucial for both the binding and the activation of the receptor, GLP-1R. We have designed analogs of histidine to investigate the molecular interactions which are responsible for these actions. We have synthesized 1-alanylpyrrole (1) and 2-alanyl-1,2,3-triazole (2) via a Michael-type addition of the herterocycles to a protected aminoacrylate. Stereochemical resolution by an acylase catalyzed hydrolysis, followed by incorporation of the appropriately protected histidine analogs into GLP-1, in place of the N-terminal histidine, gave the GLP-1 analog. These analogs were screened for binding and agonist activity against cells transfected with human GLP-1R.

 

Undergraduate Research Poster Session: Medicinal Chemistry
2:00 PM-4:00 PM, Monday, April 7, 2008 Morial Convention Center -- Hall A, Poster

Division of Chemical Education

The 235th ACS National Meeting, New Orleans, LA, April 6-10, 2008