(Journal Article): Structure-activity studies of glucagon-like peptide-l.
 
Adelhorst K, Hedegaard BB, Knudsen LB, Kirk O (Novo Nordisk A/S, Novo Alle, Bagsvaerd, Denmark.)
 
IN: J Biol Chem 1994; 269:6275-6278
Impact Factor(s) of J Biol Chem: 6.355 (2004), 6.482 (2003), 7.258 (2001)

Fulltext:    HTML  PDF

ABSTRACT: A series of analogs of glucagon-like peptide-1 (GLP-1) was made replacing each amino acid with L-alanine to identify side-chain functional groups required for interaction with the GLP-1 receptor. In the case of L-alanine being the parent amino acid, substitution was made with the amino acid found in the corresponding position in glucagon. Binding assays were performed using the cloned rat GLP-1 receptor, and receptor activation was monitored using RIN 2A18 plasma membranes. The analogs that showed the weakest receptor binding were further compared with native GLP-1 by circular dichroism spectroscopy to investigate possible conformational changes. We conclude that the side chains in positions 7, 10, 12, 13, and 15 are directly involved in the receptor interaction while positions 28 and 29 are important for GLP-1 to adapt the conformation recognized by the receptor.

TYPE OF PUBLICATION: Original article

Articles citing this article:

• Deacon CF, Johnsen AH, Holst JJ. Degradation of glucagon-like peptide-1 by human plasma in vitro yields an N-terminally truncated peptide that is a major endogenous metabolite in vivo. J Clin Endocrinol Metab 1995. 80: 952-957.
  » Diabetes OD » Disease Management » T2DM » Metabolic Control » Anti-Hyperglycemic and Anti-Ap... » Incretin Hormones » GLP-1 » Effectivity of GLP-1 in Therap... » Degradation by Dipeptidyl Pept... » Journal Article