Effect of tyrosine ionization upon biological activities of angiotensin II and two new peptide analogues.
The role of the tyrosine side-chain in the smooth muscle contracting activity of angiotensin III was investigated by determining intrinsic activities and ED50 values of [4-(3-chlorotyrosine)]angiotensin II and [4-(3-benzyltyrosine)]angiotensin II in the isolated guinea-pig ileum and rat uterus. [4-(3-chlorotyrosine)]angiotensin II activity was compared with that of angiotensin II at different pH values, in which the ratio of their degrees of phenolic ionization varied. The results indicated that deprotonation of the phenolic group hinders binding to smooth muscle cell receptors, but not triggering of the response by the hormone-receptor complex. Steric hindrance by the benzyl substituent in [4-(3-benzyltyrosine)]angiotensin II reduced both receptor-binding and triggering of the response.
Effect of tyrosine ionization upon biological activities of angiotensin II and two new peptide analogues. The role of the tyrosine side-chain in the smooth muscle contracting activity of angiotensin III was investigated by determining intrinsic activities and ED50 values of [4-(3-chlorotyrosine)]angiotensin II and [4-(3-benzyltyrosine)]angiotensin II in the isolated guinea-pig ileum and rat uterus. [4-(3-chlorotyrosine)]angiotensin II activity was compared with that of angiotensin II at different pH values, in which the ratio of their degrees of phenolic ionization varied. The results indicated that deprotonation of the phenolic group hinders binding to smooth muscle cell receptors, but not triggering of the response by the hormone-receptor complex. Steric hindrance by the benzyl substituent in [4-(3-benzyltyrosine)]angiotensin II reduced both receptor-binding and triggering of the response.