Synthesis of analogues of the Des-Phe-NH2 C-terminal hexapeptide of cholecystokinin showing gastrin antagonist activity.
Four analogues of Z-CCK-27-32-NH2, Z-Tyr(SO3-)-Met-Gly-Trp-Met-Asp-NH2, a cholecystokinin receptor antagonist have been synthesized by solution methodology. In these analogues, Z-Tyr(SO3-)-Nle-Gly-Trp-Met-Asp-NH2 16, Z-Tyr(SO3-)-Nle-Gly-Trp-Nle-Asp-NH2 17, BOC-Tyr(SO3-)-Met-Gly-Trp-Met-Asp-NH2 24 and Boc-Tyr(SO3-)-Met-Gly-Trp-Nle-Asp-NH2 25 methionyl residues were replaced by norleucyl residues. Preliminary biological activity on gastrin-induced acid secretion, in rat, are reported. These derivatives proved to antagonize the action of gastrin, with ED 50 of between 0.5 and 3 mg/kg.
Laur
J
J
Rodriguez
M
M
Aumelas
A
A
Bali
J P
JP
Martinez
J
J
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D002766:Cholecystokinin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D005745:Gastric Acidity Determination; D005753:Gastric Mucosa / Q000378:metabolism; D005755:Gastrins / Q000037:antagonists & inhibitors*; D007267:Injections; D051381:Rats
D005755:Gastrins; D002766:Cholecystokinin