CHEMICAL SYNTHESIS OF AN O-PHOSPHORYLATED TYROSINE ANALOG OF HUMAN ANGIOTENSIN-II, TYR(P)4! ANGIOTENSIN-II, AND ITS VASOCONSTRICTOR EFFECTIN INTACT SHEEP

The derivative nylmethoxy-carbonyl-O-dimethylphosphono-L-tyrosine was utilized in continuous flow solid phase synthesis to prepare the O-pho sphotyrosine analogue of human angiotensin II, Tyr(P)4! angiotensin I I. Side-chain deprotection, including the removal of the methyl phosph ate groups, as well as cleavage of the peptide from the solid support was achieved with 1 M trimethylsilylbromide-thioanisole in trifluoroac etic acid. Overall yield of purified peptide was 46%. The pressor resp onse in intact sheep to graded infusions of the synthetic Tyr(P)4! an giotensin II showed it to have similar potency to the native angiotens in II. However a prolonged, elevated mean arterial pressure was observ ed following cessation of the infusion.