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[1-N-methylisoleucine,8-threonine]-(I), [1-dimethylglycine,8-threonine]-(II), [1-guanidineacetic acid,8-threonine]-(III), des-1-aspartic acid-[8-threonine]-(IV), and [1-sarcosine,8-O-methylserine]angiotensin II (V) were synthesized by Merrifield's solid-phase procedure to study the effect of (a) substituents in position 1 on the antagonistic activity of [1-sarcosine,8-threonine]angiotensin II, and (b) a change in size and branching in position 8 of [1-sarcosine,-8-O-methylthreonine]angiotensin II. The analogues I-V caused an initial rise in blood pressure (30 min of infusion, 250 ng/kg/min in vagotomized ganglion-blocked rats) of 8.05, 11.7, 3.50, 4.5, and 11.16 mmHg. The pA2 values (rabbit aortic strips) obtained were 7.68, 7.53, 7.23, 7.53, and 9.66, and the dose ratios (in vagotomized ganglion-blocked rats infused at 250 ng/kg/min) obtained were 2.37, 4.49, 1.02, 1.47, and 24.04, respectively. The results obtained indicate that (a) the nature of the substituent in position 1 has an important influence on the biological activity of these peptides, and (b) the potency of antagonists I-IV (all less potent antagonists than [1-sarcosine,8-threonine]angiotensin II) is very much influenced by the length and branching of the side chain in position 8. The in vivo antagonistic activity of [1-sarcosine,8-O-methylthreonine]angiotensin II is reduced considerably by shortening the chain length by one carbon atom as is in V.
M C Khosla, and
M M Hall, and
H Munoz-Ramírez, and
P A Khairallah, and
F M Bumpus
January 1983,
The Journal of urology,
M C Khosla, and
M M Hall, and
H Munoz-Ramírez, and
P A Khairallah, and
F M Bumpus
September 1979,
Journal of medicinal chemistry,
M C Khosla, and
M M Hall, and
H Munoz-Ramírez, and
P A Khairallah, and
F M Bumpus
June 1974,
Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine,
M C Khosla, and
M M Hall, and
H Munoz-Ramírez, and
P A Khairallah, and
F M Bumpus
April 1973,
The Journal of pharmacology and experimental therapeutics,
M C Khosla, and
M M Hall, and
H Munoz-Ramírez, and
P A Khairallah, and
F M Bumpus
May 1976,
The Journal of physiology,
M C Khosla, and
M M Hall, and
H Munoz-Ramírez, and
P A Khairallah, and
F M Bumpus
March 1975,
Horumon to rinsho. Clinical endocrinology,
M C Khosla, and
M M Hall, and
H Munoz-Ramírez, and
P A Khairallah, and
F M Bumpus
March 1987,
Revista espanola de fisiologia,
M C Khosla, and
M M Hall, and
H Munoz-Ramírez, and
P A Khairallah, and
F M Bumpus
May 1974,
Archives internationales de pharmacodynamie et de therapie,
M C Khosla, and
M M Hall, and
H Munoz-Ramírez, and
P A Khairallah, and
F M Bumpus
September 2005,
Bioorganic & medicinal chemistry letters,
M C Khosla, and
M M Hall, and
H Munoz-Ramírez, and
P A Khairallah, and
F M Bumpus
January 1999,
Farmaco (Societa chimica italiana : 1989),
