New renin inhibitors with hydrophilic C-terminus

Pharmazie. 1999 Feb;54(2):102-6.

Abstract

Four new peptide-based renin inhibitors, Boc-Phe(4-OMe)-MePhe-AHPPA-epsilon Ahx-EA (11), Boc-Phe(4-OMe)-MeLeu-AHP-PA-epsilon Ahx-EA (15), Boc-Phe(4-OMe)-MePhe-Sta-epsilon Ahx-EA (20) and Boc-Phe(4-OMe)-MeLeu-Sta-epsilon Ahx-EA (21) have been synthesized in search of structures with improved biological properties. They were designed as compounds with moderate hydrophobicity (5.28, 4.79, 4.79 and 4.30), respectively. All synthesized inhibitors were resistant to chymotrypsin activity, all were poorly soluble in buffers pH 2.0 and pH 7.4. The inhibitory potency of renin activity in vitro of 11, 15, 20 and 21 expressed as IC50 was 7.0 x 10(-4), 7.5 x 10(-5), 6.0 x 10(-4) and 2.5 x 10(-4) M/l, respectively.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chymotrypsin
  • Drug Design
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry*
  • Hydrogen-Ion Concentration
  • Peptides / chemical synthesis*
  • Peptides / chemistry*
  • Renin / antagonists & inhibitors*
  • Solubility
  • Spectrometry, Fluorescence

Substances

  • Enzyme Inhibitors
  • Peptides
  • Chymotrypsin
  • Renin