Synthesis and biological activities of pseudopeptide analogues of the C-terminal heptapeptide of cholecystokinin. On the importance of the peptide bonds.
A series of pseudopeptide analogues of the C-terminal heptapeptide of cholecystokinin in which each peptide bond, one at a time, has been replaced by a CH2NH bond were synthesized: Z-Tyr(SO3-)-Nle-Gly-Trp-Nle-Asp psi-(CH2NH)Phe-NH2 (1), Z-Tyr(SO3-)-Nle-Gly-Trp-Nle psi (CH2NH)Asp-Phe-NH2 (2), Z-Tyr(SO3-)-Nle-Gly-Trp psi-(CH2NH)Nle-Asp-Phe-NH2 (3), Z-Tyr(SO3-)-Nle-Gly psi(CH2NH)Trp-Nle-Asp-Phe-NH2 (4), Z-Tyr(SO3-)-Nle psi-(CH2NH)Gly-Trp-Nle-Asp-Phe-NH2 (5), Z-Tyr(SO3-)-Met-Gly-Trp-Nle-Asp psi (CH2NH)Phe-NH2 (6), Z-Tyr-(SO3-)-Met-Gly-Trp-Nle psi (CH2NH)Asp-Phe-NH2 (7), Z-Tyr(SO3-)-Met-Gly-Trp psi (CH2NH)Nle-Asp-Phe-NH2 (8). These derivatives were studied for their ability to stimulate amylase release from rat pancreatic acini and to inhibit the binding of labeled CCK-9 to rat pancreatic acini and to guinea pig brain membrane CCK receptors. They were compared to the potent CCK-8 analogue Boc-Asp-Tyr(SO3-)-Nle-Gly-Trp-Nle-Asp-Phe-NH2. All of these pseudopeptides were able to stimulate amylase secretion with the same efficacy as CCK-8 but with varying potencies. These compounds were also potent in inhibiting the binding of labeled CCK-9 to CCK receptors from rat pancreatic acini and from guinea pig brain membranes.
D000681:Amylases / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D002766:Cholecystokinin / Q000031:analogs & derivatives* / Q000378:metabolism; D006168:Guinea Pigs; D008297:Male; D009842:Oligopeptides / Q000138:chemical synthesis / Q000494:pharmacology*; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011949:Receptors, Cholecystokinin / Q000378:metabolism; D012844:Sincalide / Q000031:analogs & derivatives / Q000494:pharmacology; D013329:Structure-Activity Relationship
D009842:Oligopeptides; D010446:Peptide Fragments; D011949:Receptors, Cholecystokinin; C053399:cholecystokinin 9; D002766:Cholecystokinin; C047716:cholecystokinin (27-33), tert-butyloxycarbonyl-Nle(28,31)-; D000681:Amylases; D012844:Sincalide