3914. Exendins

Description and references

Bioactive peptides isolated from the venom of Heloderma suspectum Helodermatidae (Gila monster) and H. horridum (Mexican beaded lizard). Carboxy-amidated peptides containing 39 amino acid residues; differ only at positions 2 and 3. Interact with mammalian receptors for glucagon like peptide-1 (GLP-1), a physiological regulator of insulin secretion, and exhibit similar activities. Structurally related peptides known as helospectin and helodermin have also been isolated from venom of these species and were considered exendins-1 and -2 but differ in bioactivity. Review of isoln, structure and activity: J. Eng, Mt. Sinai J. Med. 59, 147-149 (1992); J.-P. Raufman, Regul. Pept. 61, 1-18 (1996).

Derivative

Exendin-3.

Nomenclature

CAS number: 130391-54-7

Description and references

Isoln from H. horridum: J. Eng et al., J. Biol. Chem. 265, 20259 (1990).

Derivative

Exendin-4.

Nomenclature

CAS number: 141732-76-5
Exenatide; AC-2993; LY-2148568; Byetta (Amylin).

Description and references

Isoln from H. suspectum: J. Eng et al., J. Biol. Chem. 267, 7402 (1992). GLP-1 receptor binding study: R. G"oke et al., J. Biol. Chem. 268, 19650 (1993). Use as probe for human GLP-1 receptor: G. G. Chicchi et al., Peptides 18, 319 (1997). Review of pharmacology: L. L. Nielsen et al., Regul. Pept. 117, 77-88 (2004). Clinical trial in type 2 diabetes: J. B. Buse et al., Diabetes Care 27, 2628 (2004). Review of pharmacology and clinical experience: G. M. Bray, Am. J. Health Syst. Pharm. 63, 411-418 (2006).

Derivative

Exendin(9-39).

Nomenclature

CAS number: 133514-43-9
9-39-Exendin 3 (Heloderma horridum); 9-39-exendin 4; exendin (9-39) amide.

Description and references

Amino truncated fragment; specific antagonist of GLP-1 receptor. Prepn from exendin 3: J.-P. Raufman et al., J. Biol. Chem. 266, 2897 (1991). Use as GLP-1 antagonist for in vivo studies: F. Kolligs et al., Diabetes 44, 16 (1995).

Use

Biological probe.

Therapeutic Category

Antidiabetic.

Keywords

Exenatide: Antidiabetic