摘要
Based on the EDRF(endothelium derived relaxing factor)-like effects for polyarginine Arg-Arg-oH was selected as the lead compound and its derivatives Arg-Arg- OCH_3.Arg Arg-Arg-OH,HO-ArgCOCH_2CH_2COArg-OH,HO-ArgCOCH_2COArg-OH,were synthesized.These substances showed on bioassay various degrees of vasorelaxant activities. With protection for the C-terminal of Arg-Arg-OH with a methyl ester.the vasorelaxing ac- tivitv was decreased.In contrast.when the N-terminal of Arg-OH was protected with mal- onic acid or butane diacid.the biological activites were lower than those of Arg-Arg-OH due to the lowered metabolic rate.With protection of N-terminal of Arg-Arg-OH with L-Arg residue.Arg-Arg-Arg-OH was obtained,which showed a vasorelaxing activity better than that of Arg-Arg-OH.The bioactivities observed on the Wister's rats for the former com- pound become the experimental basis for prodrug design of EDRF.
依据聚精寡肽具有内皮舒张因子(EDRF)样效应的实验事实,以L-Arg-Arg-OH为先导化合物,合成了L-Arg-ArgOCH_3、L-Arg-Arg-Arg-OH、(L-Arg)_2 (CO_2) CH_2以及(L-Arg)_2(CO)_2 CH_2CH_2四种类似物。它们具有不同程度的舒血管效应。聚精二肽的羧端封锁,舒血管作用减弱。L-Arg的N端用丙二酸或丁二酸桥联,可减慢其代谢而呈现比聚精二肽弱的舒血管作用。聚精三肽的舒血管作用优于聚精二肽。
基金
This project was supported by the National Natural Science Foundation of China
