Structure‐function analysis of a series of glucagon‐like peptide‐1 analogs

• DOI: 10.1111/j.1399-3011.1998.tb00664.x
• Publication Date: 2010-08-13T13:44:58Z
• Authors: J.C. Parker; K.M. Andrews; D.M. Rescek; W. Massefski; G.C. Andrews; L.G. Contillo; R.W. Stevenson; D.H. Singleton; R.T. Suleske
• Keywords: Side chain

We have used NMR in conjunction with measurements of functional bioactivity to define the receptor-binding structure glucagon-like peptide-1 (GLP-1.) Identification important residues for binding was accomplished by substitution amino acids at sites that seemed likely, from an examination acid sequence and previously published observations, be three-dimensional (3D) molecule. receptor-bound conformation GLP-1, because it is a flexible peptide, required constraint peptide backbone into predetermined 3D structure. Constraint achieved introduction disulfide bonds specific side chain-side chain cross-links. The biological relevance synthetic each rigidified assessed measurement its ability bind receptor present on RINm5F cells elicit response, cyclic AMP production. solution structures were obtained most biologically relevant these analogs. results this study indicated necessary activity GLP-1 occupy approximately three equally-spaced regions structure, corners equilateral triangle whose sides are, minimum estimate, 12-15A.