Olverman H J, Jones A W, Mewett K N, Watkins J C
Department of Pharmacology, The Medical School, Bristol, U.K.
Neuroscience. 1988 Jul;26(1):17-31. doi: 10.1016/0306-4522(88)90124-8.
Structure/activity relations of agonists and antagonists for the N-methyl-D-aspartate receptor have been investigated by measuring the ability of a large range of substances to inhibit binding of [3H]2-amino-5-phosphonopentanoate to rat brain membranes. A major difference between optimum structures for agonist and antagonist activity lay in the differential effectiveness of sulphonic and phosphonic acid groups as the omega-acidic terminal in these two types of compound. The sulphonic acid moiety was an effective omega-acidic terminal in short chain agonists, but not in longer chain antagonists, while the phosphonic acid group was the most effective omega-acidic terminal in longer chain antagonists, but was only very weakly active in short chain agonists. It is proposed that the binding site of the omega-acidic terminal of antagonists is different from that for the omega-acidic group of agonists. Other structural features conducive to effective interaction of ligands with the receptor are discussed.
通过测量一系列物质抑制[3H]2-氨基-5-膦酸戊酯与大鼠脑膜结合的能力，对N-甲基-D-天冬氨酸受体激动剂和拮抗剂的构效关系进行了研究。激动剂和拮抗剂活性的最佳结构之间的一个主要差异在于磺酸基和膦酸基作为这两类化合物中ω-酸性末端的不同有效性。磺酸部分在短链激动剂中是有效的ω-酸性末端，但在长链拮抗剂中不是，而膦酸基团在长链拮抗剂中是最有效的ω-酸性末端，但在短链激动剂中活性非常弱。有人提出，拮抗剂的ω-酸性末端的结合位点与激动剂的ω-酸性基团的结合位点不同。还讨论了有利于配体与受体有效相互作用的其他结构特征。
