来自对第11位位置强调的P物质拮抗剂。

Antagonists of substance P from emphasis on position 11.

作者信息

Folkers K, Rosell S, Xu J C, Björkroth U, Lu Y A, Liu Y Z

出版信息

Acta Chem Scand B. 1983;37(7):623-7. doi: 10.3891/acta.chem.scand.37b-0623.

DOI:10.3891/acta.chem.scand.37b-0623

PMID:6197831

Abstract

Ten analogs of substance P (SP) were designed and synthesized. The agonist and antagonist activities against SP were assayed on the isolated guinea pig ileum. The prime designs were changes of the important Met11 to include Leu11, Thr11, D-Leu11 and D-Ala11. Step-wise designs of changing D-Arg1 and D-Pro2 to the corresponding L-configurations resulted in decreasing antagonist activity. Changing Leu11 to D-Leu11 and D-Ala11 reduced antagonist activity. [D-Arg1,D-Pro2,D-Trp7,D-Trp9,Leu11]-SP is the most potent antagonist of this group of analogs, and required a 100-fold increase in the concentration of SP to give 50% of the maximal response caused by SP.

摘要

设计并合成了10种P物质（SP）类似物。在离体豚鼠回肠上测定了它们对SP的激动剂和拮抗剂活性。主要设计是将重要的Met11替换为Leu11、Thr11、D-Leu11和D-Ala11。逐步将D-Arg1和D-Pro2替换为相应的L-构型会导致拮抗剂活性降低。将Leu11替换为D-Leu11和D-Ala11会降低拮抗剂活性。[D-Arg1,D-Pro2,D-Trp7,D-Trp9,Leu11]-SP是该组类似物中最有效的拮抗剂，需要将SP浓度提高100倍才能产生SP引起的最大反应的50%。