C(2)-Symmetric azobenzene-amino acid conjugates and their inhibition of Subtilisin Kexin Isozyme-1

Bioorg Med Chem Lett. 2010 Jul 1;20(13):3977-81. doi: 10.1016/j.bmcl.2010.04.101. Epub 2010 May 6.

Abstract

C(2)-Symmetric azobenzene-amino acid/peptide hybrids containing stable E-azo moiety have been synthesized. Upon irradiation with long wavelength UV, these compounds isomerized to the Z-form, whose thermal reisomerization to the E isomer slowed down considerably. These compounds exhibited in vitro moderate to strong inhibition of mammalian cellular protease Subtilisin Kexin Isozyme-1, also called Site 1 Protease, which plays vital roles in cholesterol synthesis, lipid metabolism, bone formation, and viral infections.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / chemistry
  • Amino Acids / pharmacology*
  • Animals
  • Azo Compounds / chemistry
  • Azo Compounds / pharmacology*
  • Crystallography, X-Ray
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Peptides / chemical synthesis
  • Peptides / chemistry
  • Peptides / pharmacology*
  • Proprotein Convertases / antagonists & inhibitors*
  • Serine Endopeptidases
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Amino Acids
  • Azo Compounds
  • Enzyme Inhibitors
  • Peptides
  • Proprotein Convertases
  • Serine Endopeptidases
  • membrane-bound transcription factor peptidase, site 1
  • azobenzene