title: Binding of cholecystokinin-8 (CCK-8) peptide derivatives to CCKA and CCKB receptors.
abstract: The structural requirements for the selective binding of cholecystokinin-8 (CCK-8)-related peptides to peripheral (CCKA) receptors are not sufficiently understood. In this study, the interaction of a series of newly shortened analogues of CCK-8 with both receptor subtypes was analyzed by displacement studies using [3H]-CCK-8 and 125I-Bolton-Hunter (BH)-CCK-8 as radioligands. The pentapeptide derivative of CCK-8, succinyl-Tyr (SO3H)-Met-Gly-Trp-Met-phenethylamide, was found to bind selectively with high affinity to the CCKA receptor. The replacement of Met28 and/or Met31 by norleucine and of L-Trp30 by its D-analogue had no significant effect on the binding properties of the peptide. Further C-terminal shortening resulted in a drastic loss of affinity and selectivity of the CCK receptor binding.
authors.affiliation: Institute of Pharmacology and Toxicology Medical Faculty (Charité), Humboldt University, Berlin, F.R.G.
authors.forename: U
authors.initials: U
authors.lastname: Schäfer
authors.forename: R
authors.initials: R
authors.lastname: Harhammer
authors.forename: M
authors.initials: M
authors.lastname: Boomgaarden
authors.forename: R
authors.initials: R
authors.lastname: Sohr
authors.forename: T
authors.initials: T
authors.lastname: Ott
authors.forename: P
authors.initials: P
authors.lastname: Henklein
authors.forename: H
authors.initials: H
authors.lastname: Repke
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D007202:Indicators and Reagents; D007700:Kinetics; D008297:Male; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011949:Receptors, Cholecystokinin / Q000378:metabolism*; D012844:Sincalide / Q000031:analogs & derivatives* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013388:Succinimides / Q000378:metabolism
chemical_list: C044758:Bolton Hunter-cholecystokinin octapeptide; D007202:Indicators and Reagents; D010446:Peptide Fragments; D011949:Receptors, Cholecystokinin; D013388:Succinimides; D012844:Sincalide