Cheronis J C, Whalley E T, Blodgett J K
Cortech, Inc., Denver, Colorado 80221.
Agents Actions Suppl. 1992;38 ( Pt 1):551-8. doi: 10.1007/978-3-0348-7321-5_67.
A systematic study on dimerization of the bradykinin (BK) antagonist D-Arg0-Arg1-Pro2-Hyp3-Gly4-Phe5-Ser6-D-Phe 7-Leu8-Arg9 has been performed. Several of the dimeric BK antagonists displayed remarkable activities and long durations of action. Rank order of antagonist potency as a function of dimerization position is as follows: rat uterus 6 > 5 > 0 > 2 > 1 > 3 >> 4,7,8,9; guinea pig ileum 6 > 5 > 3 > 2 > 1 > 0 >> 4,7,8,9. These results suggest that the development of BK antagonists of significant therapeutic potential may be possible using a dimerization strategy that can overcome the heretofore limiting problems of potency and in vivo duration of action.
已对缓激肽（BK）拮抗剂D-Arg0-Arg1-Pro2-Hyp3-Gly4-Phe5-Ser6-D-Phe 7-Leu8-Arg9的二聚化进行了系统研究。几种二聚体BK拮抗剂表现出显著的活性和长效作用。作为二聚化位置函数的拮抗剂效力排序如下：大鼠子宫6 > 5 > 0 > 2 > 1 > 3 >> 4,7,8,9；豚鼠回肠6 > 5 > 3 > 2 > 1 > 0 >> 4,7,8,9。这些结果表明，使用一种能够克服迄今为止效力和体内作用持续时间方面的限制问题的二聚化策略，有可能开发出具有显著治疗潜力的BK拮抗剂。
