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.
Kitas
E A
EA
Howard Florey Institute, University of Melbourne, Parkville, Victoria, Australia.
Johns
R B
RB
May
C N
CN
Tregear
G W
GW
Wade
J D
JD
D000595:Amino Acid Sequence; D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006801:Humans; D008969:Molecular Sequence Data; D010766:Phosphorylation; D012756:Sheep; D014443:Tyrosine / Q000031:analogs & derivatives*; D000092502:Renin Inhibitors
D000804:Angiotensin II; D014443:Tyrosine; D000092502:Renin Inhibitors; C067268:phosphotyrosylangiotensin II