title: Synthesis of human CCK26-33 and CCK-33 related analogues on 2,4-DMBHA and TMBHA.
abstract: New analogues of human cholecystokinin in which the Tyr(SO3H) has been replaced by Phe(p-CH2SO3Na), methionines by norleucines, and tryptophan by 2-naphthylalanine([Phe(p-CH2- SO3Na)27,Nle28,31,Nal30]-CCK26-33 and [Phe(p-CH2SO3Na)27,Nle7,28,31,Nal30]-CCK-33) were synthesized by Fmoc solid phase methodology on two different resins (2,4- dimethoxybenzhydrylamine- and 4-(benzyloxy)-2',4'-dimethoxybenzhydrylamine resins, 2,4-DMBHA and TMBHA resins, respectively). While the syntheses on the TMBHA appeared to be more sluggish than those carried out on the 2,4-DMBHA, both final crude products were of equivalent relative purity and after purification gave approximately the same final yields of analogues estimated to have a purity greater than 93% using RPHPLC and CZE. The peptides were further characterized by amino acid analysis and LSIMS. Phe(p-CH2SO3Na)27,Nle7,28,31,Nal30]-CCK-33 was submitted to 33 Edman cycles and shown to be the desired product with less than 3% preview. Both analogues were tested for their ability to stimulate amylase release from isolated rat pancreatic acini. In this assay, [Phe(p-CH2SO3Na)27,Nle28,31,Nal30]-CCK26-33 and Phe(p-CH2SO3Na)27,Nle7,28,31,Nal30]-CCK-33 were 10 and 30 times less potent than CCK-8, respectively.
authors.affiliation: Clayton Foundation Laboratories for Peptide Biology, Salk Institute for Biological Studies, La Jolla, California 92037.
authors.forename: M T
authors.initials: MT
authors.lastname: Miranda
authors.forename: R A
authors.initials: RA
authors.lastname: Liddle
authors.forename: J E
authors.initials: JE
authors.lastname: Rivier
mesh_terms: D000595:Amino Acid Sequence; D000681:Amylases / Q000378:metabolism; D000818:Animals; D001559:Benzhydryl Compounds; D002766:Cholecystokinin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D008969:Molecular Sequence Data; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D012116:Resins, Plant; D012844:Sincalide / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D001559:Benzhydryl Compounds; D012116:Resins, Plant; C081668:2,4-dimethoxybenzhydrylamine; C081669:4-(benzoyloxy)-2',4'-dimethoxybenzhydrylamine; C044201:cholecystokinin (26-33); D002766:Cholecystokinin; D000681:Amylases; D012844:Sincalide