Structural requirements for biological activity of glucagon‐like peptide‐I

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Abstract
Glucagon-like peptide-I (GLP-I) is encoded together with glucagon by the glucagon gene and is related in its structure to the glucagon-secretin family of peptides. Three of the predicted forms of the peptide, a 37-residue long GLP-I(1–37), a 31-residue GLP-I(7–37) and a 30-residue GLP-I(7–36) amide as well as three analogs des [Gly37, Arg36] GLP-I(7–37), des [Gly37, Arg36, Gly35] GLP-I(7–37) and des [His7] GLP-I(7–37) were synthesized by the stepwise solid phase method. These synthetic peptides were used to define the structural domains required for the binding of GLP-I to the pancreatic beta cell. The competitive binding experiments showed that both the amino and carboxyl terminal domains of the molecule contribute to GLP-I binding. In these experiments glucagon, another peptide that stimulates insulin secretion, was a weak full agonist of GLP-I binding. Results from these studies provide further characterization of the physiological role of this new peptide.