Development of lipopeptides for inhibiting 20S proteasomes

Bioorg Med Chem Lett. 2006 Jun 15;16(12):3277-81. doi: 10.1016/j.bmcl.2006.03.033. Epub 2006 Apr 21.

Abstract

Proteasomes are responsible for the cytoplasmic turnover of the vast majority of proteins including regulatory proteins. We have synthesized lipopeptides a new class of non-covalent inhibitors of the 20S proteasome and assayed their inhibitory capacities. Their ability to inhibit at micromolar concentrations chymotrypsin-like and post-acid activities depends on peptide length (3 or 6 amino acids), sequence (presence of a positively or negatively charged amino acid), and alkyl chain length (C6-C18). These structural features could be varied to selectively inhibit one or more of the three proteasome activities.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Lipoproteins / chemical synthesis
  • Lipoproteins / chemistry*
  • Lipoproteins / pharmacology*
  • Molecular Structure
  • Peptide Hydrolases / metabolism
  • Peptides / chemical synthesis
  • Peptides / chemistry*
  • Peptides / pharmacology*
  • Proteasome Endopeptidase Complex / metabolism
  • Proteasome Inhibitors*
  • Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • Lipoproteins
  • Peptides
  • Proteasome Inhibitors
  • semen liquefaction factor
  • Peptide Hydrolases
  • Proteasome Endopeptidase Complex