Angiotensin II. Synthesis and Biological Activity of 6-(1-Methylhistidine) and 6-(3-Methylhistidine) Analogs

The synthesis and purification of [1-MeHis⁶]angiotensin II and [3-MeHis⁶]angiotensin II are described. The [3-MeHis⁶] analog was about 5% as active as angiotensin II in contracting isolated smooth muscle preparations, as a vasopressor agent, and in releasing prostaglandin from isolated perfused rabbit kidneys. [1-MeHis⁶]angiotensin II had little or no biological activity. Neither of the analogs had any antagonistic activity. The effect of pH on the uterine sensitivity to histidine analogs and to N-acetyl angiotensin II indicates that neither the state of protonation of the a-amino or imidazole groups nor a conformation charge associated with titration of these groups accounts for the increased sensitivity of the uterus to angiotensin at alkaline pH.