Amino-acids and peptides. Part XXXII. A simplified synthesis of bradykinin by use of the picolyl ester method

Abstract

The use of 4-picolyl esters for the facilitation of peptide synthesis has been further examined in a synthesis of protected bradykinin (overall yield 42%). Hydrogenation gave bradykinin with full biological activity. Prolonged hydrogenation over palladium caused partial reduction of the phenylalanine residues, and complete reduction was effected over palladium and platinum. The product, which the amino-acid analysis indicated was [5,8-β-cyclo-hexylalanine]-bradykinin, showed high bradykinin-like activity in the guinea-pig ileum test, suggesting that aromatic residues are not essential for such activity, but confirmation of this conclusion must await a full biological comparison with bradykinin itself.