Amino-acids and peptides. Part 48. Synthesis of bradykinyl-chloromethane

An analogue of the local tissue hormone bradykinin, in which the terminal carboxy group is replaced by a chloromethyl ketone function, has been synthesised. A protected octapeptide, synthesised by the picolyl ester "handle" procedure, was coupled to N delta, N omega-dibenzyloxycarbonyl-L-arginyl-choromethane; the product was deprotected by hydrogen fluoride, giving bradykinyl-chloromethane. The preservation of the reactive chloromethyl ketone group and the entire structure of the product was confirmed by fast atom bombardment mass spectrometry. On the rat uterus and guinea-pig ileum bradykinyl-chloromethane was a weak agonist showing no antagonism of responses to bradykinin.