Chemical synthesis of an O-phosphorylated tyrosine analogue of human angiotensin II, [Tyr(P)4] angiotensin II, and its vasoconstrictor effect in intact sheep

The derivative N alpha-fluorenylmethoxy-carbonyl-O-dimethylphosphono-L-tyrosi ne was utilized in continuous-flow solid-phase synthesis to prepare the O-phosphotyrosine analogue of human angiotensin II, [Tyr(P)4] angiotensin II. Side-chain deprotection, including the removal of the methyl phosphate groups, as well as cleavage of the peptide from the solid support was achieved with 1 M trimethylsilyl-bromide-thioanisole in trifluoroacetic acid. Overall yield of purified peptide was 46%. The pressor response in intact sheep to graded infusions of the synthetic [Tyr(P)4] angiotensin II showed it to have similar potency to the native angiotensin II. However, a prolonged, elevated mean arterial pressure was observed following cessation of the infusion.