Syntheses and Biological Activities of Endothelin-1 Analogs

概要

論文の詳細を見る
Endothelin-1 analogs replaced by various amino acids at position 21,namely [X^<21>]-ET-1,were synthesized, and their agonistic vasoconstrictor activity on rat thoracic aortic strips and receptor binding activity on rat brain membrane fraction were examined to elucidate their structure-activity relationship. The vasoconstrictor activities of [Tyr^<21>]- and [Phe^<21>]-ET-1 were one order of magnitude smaller than that of ET-1,and those of [His^<21>]-, [Gly^<21>]-, [Ser^<21>]-, [Ala^<21>]- and [Lys^<21>]-ET-1 were more than two orders of magnitude smaller than that of ET-1. On the other hand, the replacements by Ile, Glu, Gln and Pro resulted in distinguished losses of the vasoconstrictor activities. In addition, preincubation with these analogs did not blunt ET-1-induced vasoconstriction and showed no antagonistic activity. The binding inhibitory activities of these analogs against ^<125>I-ET-1 were approximately conformable to the vasoconstrictor activities with only a slight exception. These findings demonstrate that the phenyl group at position 21 is important for both the vasoconstrictor activity and the receptor binding activity.
社団法人日本薬学会の論文
1991-11-25