N-(.alpha.-hydroxyalkanoyl) derivatives of Leu-Val-Phe-OCH3 as inhibitors of renin
- 1 June 1980
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 23 (6) , 666-669
- https://doi.org/10.1021/jm00180a017
Abstract
The following N-(.alpha.-hydroxyalkanoyl) derivatives of Leu-Val-Phe-OCH3 leucylvalylphenylalanine methyl ester were synthesized and tested for their ability to inhibit human amniotic renin: D- and L-.alpha.-hydroxyisocaproyl-Leu-Val-Phe-OCH3, D- and L-.alpha.-hydroxyisovaleryl-Leu-Val-Phe-OCH3, L-2-hydroxy-3-phenylpropanoyl-Leu-Val-Phe-OCH3, and D- and L-.alpha.-hydroxyphenylacetyl-Leu-Val-Phe-OCH3. Analysis of the compounds through the use of Dixon plots showed all of the compounds to be competitive inhibitors of renin. All but D-.alpha.-hydroxyisovaleryl-Leu-Val-Phe-OCH3 were more active than the known tetrapeptide inhibitor Leu-Leu-Val-Phe-OCH3. The 2 most active compounds of the series were L-.alpha.-hydroxyisocaproyl-Leu-Val-Phe-OCH3 (Ki [inhibition constant] = 0.23 mM) and L-.alpha.-hydroxyisovaleryl-Leu-Val-Phe-OCH3 (Ki = 0.3 mM).This publication has 3 references indexed in Scilit:
- Partial purification and chromatographic properties of inactive renin from human amniotic fluidBiochemical Pharmacology, 1979
- Mode of inhibition of acid proteases by pepstatin.Journal of Biological Chemistry, 1976
- 196. Über den enzymatischen Abbau von l-α -Oxysäuren)Helvetica Chimica Acta, 1945