Charpentier B, Durieux C, Pelaprat D, Dor A, Reibaud M, Blanchard J C, Roques B P
Département de Chimie Organique, U 266 INSERM, UA 498 CNRS, Paris, France.
Peptides. 1988 Jul-Aug;9(4):835-41. doi: 10.1016/0196-9781(88)90130-1.
Based on the results of the in vitro metabolism of CCK8 by various peptidases, we have synthesized three CCK analogs: Boc-Tyr(SO3H)-Nle-Gly-Trp-(N- Me)Nle-Asp-Phe-NH2 (compound I), Boc-Tyr(SO3H)-gNle-mGly-Trp-Nle-Asp-Phe-Nh2 (compound II), Boc-Tyr(SO3H)-gNle-mGly-Trp-(N-Me)Nle-Asp-Phe-NH2 (compound III). In in vitro enzymatic degradation studies, these compounds showed a high stability toward either enkephalinase or the enzymes present in crude rat brain membranes preparations. Moreover, in binding studies on guinea pig tissues, these CCK-related peptides were characterized by high apparent affinities for brain CCK receptors and by a broader range of affinities for pancreatic CCK receptors. This broad range of affinities was reflected by their pharmacological potencies in the guinea pig pancreatic amylase release and ileum contraction assays. These enzyme-resistant CCK analogs provide therefore valuable tools to investigate the pharmacology of CCK.
基于各种肽酶对CCK8的体外代谢结果，我们合成了三种CCK类似物：Boc-Tyr(SO3H)-Nle-Gly-Trp-(N-Me)Nle-Asp-Phe-NH2（化合物I）、Boc-Tyr(SO3H)-gNle-mGly-Trp-Nle-Asp-Phe-Nh2（化合物II）、Boc-Tyr(SO3H)-gNle-mGly-Trp-(N-Me)Nle-Asp-Phe-NH2（化合物III）。在体外酶降解研究中，这些化合物对脑啡肽酶或大鼠脑膜粗制品中存在的酶均表现出高稳定性。此外，在豚鼠组织的结合研究中，这些CCK相关肽的特点是对脑CCK受体具有高表观亲和力，对胰腺CCK受体具有更广泛的亲和力。这种广泛的亲和力在豚鼠胰腺淀粉酶释放和回肠收缩试验中的药理效力上得到了体现。因此，这些抗酶CCK类似物为研究CCK的药理学提供了有价值的工具。
