Consideration of the kinetics of the evaporation of peptides leads to two approaches to volatility enhancement. An obvious direction to take is to attempt to reduce the energy of bonding of molecules to surfaces by dispersal onto surfaces which are relatively inert.
These findings strongly support the viral safety of IGIV prepared by this method and show a significant added measure of virus safety associated with pasteurization of this preparation.
The octapeptide analogues 8-Cys-AII, 8-Ile-AII, 4-Phe-8-Tyr-AII, and pfluoro-4-Phe-AII were potent competitive antagonists of angiotensin I and II (AI and All) in rat uterus strips, whereas the decapeptide analogues 4-Fhe-8-Tyr-AI and 8-He-AI were weak antagonists. 8-Cys-AII and 8-Ile-AII were potent antagonists of the rise in blood pressure induced by angiotensin, although 4-Phe-8-Tyr-AII and p-fluoro-4-Phe-AII were less potent antagonists. AI was rapidly converted and was equipotent to All in vivo, but 8-Ile-AI was a hundred times less potent than 8-Ile-AII. However, some conversion of 8-Ile-AI did occur, since SQ 20881 (an inhibitor of angiotensin-converting enzyme) markedly diminished the All antagonistic action of 8-Ile-AI. The decapeptides AI, 8-Ile-AI, and 4-Phe-8-Tyr-AI were potent competitive antagonists of the hydrolysis of hippurylhistidylleucine by converting enzyme in vitro. Infusion of the octapeptide and the decapeptide angiotensin analogues resulted in a significant lowering of the blood pressure in anesthetized rats treated with phenoxybenzamine and propranolol and made acutely hypertensive by unclamping a renal pedicle that had been temporarily occluded. The decapeptide analogues, therefore, can function as inhibitors of angiotensinconverting enzyme and simultaneously generate octapeptide antagonists in vivo.
KEY WORDSrenal hypertension p-fluoro-4-Phe-angiotensin II 8-Cys-angiotensin II 8-Ile-angiotensin H converting enzyme 4-Phe-8-Tyr-angiotensin II p-fluoro-8-Phe-angiotensin II 4-Phe-8-Tyr-angiotensin I 8-Ile-angiotensin I SQ 20881 venom peptide rat uterus rabbit lung• The decapeptide angiotensin I (AI) possesses minimal biological activity, but the octapeptide angiotensin II (All) is an extremely potent substance with a wide range o£ From the
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