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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Novel renin inhibitors containing the amino acid statine.

The proteolytic enzyme renin (EC3.4.99.19) cleaves the protein substrate angiotensinogen to yield angiotensin I, the decapeptide substrate transformed by converting enzyme into the pressor substance angiotensin II. Although the contribution of this pathway to the maintenance of normal blood pressure is unclear, it seems to be a major factor in various hypertensive states. Important progress in the control of hypertension has been achieved by development of the potent inhibitors SQ-14,225 (captopril) and MK-421 (enalapril maleate), which block the generation of angiotensin II by the inhibition of angiotensin converting enzyme. An attractive alternative to the inhibition of converting enzyme would be the blockade of the preceding step in the cascade, the renin reaction. We report here new highly potent (IC50 = 10(-9)-10(-8) M) competitive inhibitors of renin in which statine, (3S,4S)-4-amino-3-hydroxy-6-methylheptanoic acid, is incorporated into analogues of the pig renin substrate (Fig. 1).[1]


  1. Novel renin inhibitors containing the amino acid statine. Boger, J., Lohr, N.S., Ulm, E.H., Poe, M., Blaine, E.H., Fanelli, G.M., Lin, T.Y., Payne, L.S., Schorn, T.W., LaMont, B.I., Vassil, T.C., Stabilito, I.I., Veber, D.F., Rich, D.H., Bopari, A.S. Nature (1983) [Pubmed]
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