title: Tetrapeptide CCK-A agonists: effect of backbone N-methylations on in vitro and in vivo CCK activity.
abstract: N-Methylation of backbone amide bonds was conducted on a tetrapeptide that had been identified previously (Shiosaki, K.; et al. J. Med. Chem. 1991, 34, 2387-2842) as a potent and selective CCK-A agonist. N alpha-Methylation at the position corresponding to Asp32 (CCK-33 numbering) was consistent with high affinity, efficacy, and selectivity for the CCK-A receptor. Combination of this (N-Me)Asp with the (N-Me)Phe modification also provided a highly active analogue. The observation of parallel structure-binding affinity profiles with respect to sites of N-methylation in the C-terminal regions of tetrapeptide vs heptapeptide CCK analogues suggests that the two series interact similarly with the CCK-A receptor.
authors.affiliation: Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, Illinois 60064.
authors.forename: M W
authors.initials: MW
authors.lastname: Holladay
authors.forename: H
authors.initials: H
authors.lastname: Kopecka
authors.forename: T R
authors.initials: TR
authors.lastname: Miller
authors.forename: L
authors.initials: L
authors.lastname: Bednarz
authors.forename: A L
authors.initials: AL
authors.lastname: Nikkel
authors.forename: B R
authors.initials: BR
authors.lastname: Bianchi
authors.forename: D G
authors.initials: DG
authors.lastname: Witte
authors.forename: K
authors.initials: K
authors.lastname: Shiosaki
authors.forename: C W
authors.initials: CW
authors.lastname: Lin
authors.forename: K E
authors.initials: KE
authors.lastname: Asin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002766:Cholecystokinin / Q000031:analogs & derivatives* / Q000737:chemistry; D004435:Eating / Q000187:drug effects; D008745:Methylation; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011949:Receptors, Cholecystokinin / Q000378:metabolism; D013329:Structure-Activity Relationship; D013431:Sulfates / Q000378:metabolism
chemical_list: D009842:Oligopeptides; D011949:Receptors, Cholecystokinin; D013431:Sulfates; D002766:Cholecystokinin