Lavielle S, Chassaing G, Loeuillet D, Convert O, Torrens Y, Beaujouan J C, Saffroy M, Petitet F, Bergström L, Glowinski J
Laboratoire de Chimie Organique Biologique, CNRS UA 493, Paris, France.
Fundam Clin Pharmacol. 1990;4(3):257-68. doi: 10.1111/j.1472-8206.1990.tb00493.x.
Three types of binding sites for the mammalian tachykinins, ie Substance P (SP) Neurokinin A (NKA) and Neurokinin B (NKB), have been found in both the central and peripheral nervous systems. Substance P binds to the NK-1 subclass of binding site while NKA and NKB are less selective endogenous ligands, which preferentially interact with the NK-2 and NK-3 subclasses of binding sites, respectively. Complementary strategies, including 3-dimensional structure analysis by NMR spectroscopy and structure-activity relationship led to the design of selective agonists of these binding sites. [Pro9] SP, [Pro10] SP and the cyclic analogues [Cys3,6, Tyr8, Pro9] SP and [Cys3,6, Tyr8, Pro10] SP are selective NK-1 agonists. [Lys5] NKA(4-10) is a water soluble NK-2 potent agonist. Finally, [Pro7] NKB, which completely discriminates NK-2 and NK-3 binding sites, is a water-soluble NK-3 selective agonist.
在中枢和外周神经系统中均发现了三种哺乳动物速激肽的结合位点，即P物质（SP）、神经激肽A（NKA）和神经激肽B（NKB）。P物质与结合位点的NK-1亚类结合，而NKA和NKB是选择性较低的内源性配体，它们分别优先与结合位点的NK-2和NK-3亚类相互作用。包括通过核磁共振光谱进行三维结构分析和构效关系在内的互补策略，促成了这些结合位点选择性激动剂的设计。[Pro9]SP、[Pro10]SP以及环类似物[Cys3,6,Tyr8,Pro9]SP和[Cys3,6,Tyr8,Pro10]SP是选择性NK-1激动剂。[Lys5]NKA(4-10)是一种水溶性NK-2强效激动剂。最后，完全区分NK-2和NK-3结合位点的[Pro7]NKB是一种水溶性NK-3选择性激动剂。
