Exenatide

Exenatide is a 39-residue peptide with an N-terminal histidine and a C-terminal serine amide, originally isolated from Heloderma suspectum venom and characterized as a member of the glucagon superfamily.

Exenatide is the synthetic form of exendin-4, a peptide isolated from the venom of the lizard Heloderma suspectum. Exendin-3, isolated from Heloderma horridum, differs by two substitutions at positions 2 and 3. Both are members of the glucagon superfamily.

Declared aliases and development codes: Exendin-4.

Exenatide is synthetic exendin-4 and shares GLP-1 receptor agonism with the native hormone. Its direct sequence parent is exendin-4, a peptide of non-human origin, not human GLP-1. Shared receptor activity and general architecture do not establish human GLP-1 scaffold ancestry, and no human-GLP-1 substitution table applies to it. The related GLP-1(7-36) amide entry is a native receptor comparator only, not a structural parent. The isolation report describes a 39-amino-acid peptide recovered using a sequencing assay for peptides bearing an amino-terminal histidine. Exendin-4 differs from exendin-3 by two amino acid substitutions, Gly2-Glu3 in place of Ser2-Asp3, and is otherwise identical; the report notes that this difference is sufficient to change the observed bioactivity profile. In dispersed guinea pig pancreatic acini, exendin-4 produced a monophasic increase in cAMP that was progressively inhibited by the antagonist exendin-(9-39) amide, whereas exendin-3 produced a biphasic response and interacted additionally with VIP receptors.

Terminal features: C-terminal serine amide.