Synthesis of the vasoactive intestinal peptide (VIP): IV. The sequence 14–28

Abstract

A protected pentadecapeptide with the C-terminal sequence of the vasoactive intestinal peptide (VIP) was prepared by coupling the tetrapeptide derivative t-butyloxycarbonyl- l-arginyl- N ε-benzyloxycarbonyl- l-lysyl- l-glutaminyl- l-methionine azide to the partially deprotected hendecapeptide l-alanyl- l-valyl- N ε-benzyloxycarbonyl- l-lysyl- N ε-benzyloxycarbonyl- l-lysyl- l-tyrosyl- l-leucyl- l- asparaginyl- l-seryl- l-isoleucyl- l-leucyl- l-asparaginamide. The preparation of the protected tetradecapeptide t-butyloxycarbonyl- N ε-benzyloxycarbonyl- l-lysyl- l-glutaminyl- l-methionyl- l-alanyl- l-valyl- N ε- benzyloxycarbonyl- l-lysyl- N ε-benzyloxycarbonyl- l-lysyl- l-tyrosyl- l-leucyl- l-asparaginyl- l-seryl- l-isoleucyl- l-leucyl- l-asparaginamide is also reported. The protecting groups were removed from samples of the tetradeca- and pentadecapeptides. The resulting free peptides showed, although at high dose levels, increase of visceral blood flow and reduction of blood pressure in the dog, and also relaxation of different smooth muscle preparations, which are the characteristic biological activities of VIP.