Exploring GLP-1R activation using a metal chelated nitrilotriacetic acid derivative

CHED 574

Elizabeth H Kelley, ekelley@wellesley.edu1, Margaret W. Thompson, mthomps2@wellesley.edu1, David R. Haines, DHaines@Wellesley.edu1, and Martin Beinborn, Mbeinborn@Lifespan.org2. (1) Department of Chemistry, Wellesley College, 106 Central Street, Wellesley, MA 02481, (2) Department of Medicine, New England Medical Center, Molecular Pharmacology Research Center, 750 Washington St., #7703, Boston, MA 02111
Glucagon-like peptide 1 (GLP-1) is a small peptide that binds to its receptor (GLP-1R) to initiate the production and release of insulin. Attachment of the N-terminal 14 amino acids of GLP-1 to the N-terminus of GLP-1R results in a constitutively activated receptor. We are exploring delivery of this N-14 amino acid peptide to GLP-1R via complexation of a peptide containing the nitrilotriacetic acid (NTA) nickel complex to poly-His regions incorporated in various locations in the GLP-1R. The NTA-peptide is prepared via dialkylation of a protected lysine, coupling of the NTA to glutamic acid and appropriate protection of the glutamic acid for incorporation into solid phase peptide synthesis. Attachment of the NTA to the N-14 fragment of GLP-1 allows us to test the necessary NTA-poly-His region proximities to the activating region of GLP-1R. The synthesis of the NTA containing peptide, as well as the preliminary biological results will be discussed.

 

Undergraduate Research Poster Session: Organic Chemistry
11:00 AM-1:00 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