Peptide Knowledge Center
4 important structural features of Exenatide
Exenatide is a peptide containing 39 amino acid residues, and has a homology of up to 50% with glucagon-like peptide-1 (GLP-1), which not only has the effect of promoting insulin secretion in vivo , and the half-life in vivo is much higher than that of natural GLP-1. As the first clinically used incretin-like drug, its hypoglycemic effect is significant, and it will stop when blood sugar is reduced to normal, and will not cause hypoglycemia. .
Biophysical and pharmacological studies have shown that the structure of exenatide has the following characteristics:
① The N-terminal His9-Asp17 amino acid fragment is in a random coiled state, which is the main region for activating the receptor.
② The stability of the α helix formed in the molecule is stronger than that of GLP-1, which is due to the formation of intramolecular hydrogen bonds between Glu24/Glu25 and Arg28 and between Glu32 and Lys35 to stabilize the helix, while GLP-1 has no corresponding α-helix. Intramolecular hydrogen bonding.
③ There are significant polar and non-polar amino acids, and this amphiphilic property enhances the binding strength to the extracellular domain of the receptor. ④ Exenatide has 8 more amino acid residues than GLP-1. NMR studies show that Ser40-Ser48 at the C-terminus forms a stable cage-like conformation around Trp33, which is favorable for receptor binding.