Synthesis of [l-Isoleucine-, 3-Proline-, and 5-Alanine ]-angiotensins 11

Abstract

1-Isoleucine,5-isoleucine]-angiotensin II and [3-proline,5-isoleucine]-angiotensin II were synthesized by the solid-phase method using dicyclohexylcarbodiimide as the condensing agent. The formation of the arginyl-proline bond was extremely difficult under conditions used. The former had about 25% pressor and 50% oxytocic activities giving further evidence the acidity of the j3-carboxyl is unnecessary. The latter possessed 40% pressor and 80% oxytocic activities of the parent angiotensin. This relatively high biological activity was surprising because of the limitation on possible peptide conformations imposed by this cyclic amino acid. [5-Alanine]-angiotensin II was prepared by solid phase using N-ethyl-5-phenylisoxazolium-3-sulfonate as the condensing agent. This peptide possessed approximately 5% of pressor activity of angiotensin II indicating the importance of branched side chain of valine or isoleucine occurring naturally in this position.