The selectivity of statine-based inhibitors against various human aspartic proteinases
- 1 February 1990
- journal article
- research article
- Published by Portland Press Ltd. in Biochemical Journal
- Vol. 265 (3) , 871-878
- https://doi.org/10.1042/bj2650871
Abstract
The interactions of five human enzymes (renin, pepsin, gastricsin, cathepsin D and cathepsin E) and the aspartic proteinase from Endothia parasitica with several series of synthetic inhibitors were examined. All of the inhibitors contained the dipeptide analogue statine or its phenylalanine or cyclohexylalanine homologues in the P1-P1'' positions. The residues occupying the peripheral sub-sites (P4 to P3'') were varied systematically and inhibitory constants were determined for the interactions with each of the proteinases. Inhibitors were elucidated that specifically inhibited human renin and did not affect any of the other human enzymes or the fungal proteinase. With suitable selection of residues to occupy individual sub-sites, effective inhibitors of specific human aspartic proteinases may now be designed.This publication has 32 references indexed in Scilit:
- Effective blocking of HIV‐1 proteinase activity by characteristic inhibitors of aspartic proteinasesFEBS Letters, 1989
- A novel nonpeptidic, orally active renin inhibitorBiochemical and Biophysical Research Communications, 1989
- A highly potent and long-acting oral inhibitor of human renin.Hypertension, 1988
- New human renin inhibitors containing an unnatural amino acid, norstatineJournal of Medicinal Chemistry, 1988
- New inhibitors of human renin that contain novel Leu-Val replacements. Examination of the P1 siteJournal of Medicinal Chemistry, 1988
- Inhibition of porcine pepsin by two substrate analogs containing statine. The effect of histidine at the P2 subsite on the inhibition of aspartic proteinasesJournal of Medicinal Chemistry, 1988
- The pH dependence of the hydrolysis of chromogenic substrates of the type, Lys-Pro-Xaa-Yaa-Phe-(NO2)Phe-Arg-Leu, by selected aspartic proteinases: evidence for specific interactions in subsites S3 and S2Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology, 1987
- Renin inhibitors. Syntheses of subnanomolar, competitive, transition-state analog inhibitors containing a novel analog of statineJournal of Medicinal Chemistry, 1985
- Synthesis of analogs of the carboxyl protease inhibitor pepstatin. Effect of structure in subsite P3 on inhibition of pepsinJournal of Medicinal Chemistry, 1982
- The amino terminal amino acid sequence of human angiotensinogenBiochemical and Biophysical Research Communications, 1981