Schäfer U, Harhammer R, Boomgaarden M, Sohr R, Ott T, Henklein P, Repke H
Institute of Pharmacology and Toxicology Medical Faculty (Charité), Humboldt University, Berlin, F.R.G.
J Neurochem. 1994 Apr;62(4):1426-31. doi: 10.1046/j.1471-4159.1994.62041426.x.
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.
胆囊收缩素-8（CCK-8）相关肽与外周（CCKA）受体选择性结合的结构要求尚未得到充分了解。在本研究中，使用[3H]-CCK-8和125I-博尔顿-亨特（BH）-CCK-8作为放射性配体，通过置换研究分析了一系列新的缩短的CCK-8类似物与两种受体亚型的相互作用。发现CCK-8的五肽衍生物琥珀酰-Tyr（SO3H）-Met-Gly-Trp-Met-苯乙酰胺以高亲和力选择性地与CCKA受体结合。用正亮氨酸取代Met28和/或Met31以及用其D-类似物取代L-Trp30对该肽的结合特性没有显著影响。进一步缩短C末端导致CCK受体结合的亲和力和选择性急剧丧失。
