Design of cell-permeable, fluorescent activity-based probes for the lysosomal cysteine protease asparaginyl endopeptidase (AEP)/legumain

Bioorg Med Chem Lett. 2007 Feb 1;17(3):649-53. doi: 10.1016/j.bmcl.2006.10.100. Epub 2006 Nov 6.

Abstract

Asparaginyl endopeptidase (AEP), also known as legumain, is a cysteine protease that has been ascribed roles in antigen presentation yet its exact role in human biology remains poorly understood. We report here, the use of a positional scanning combinatorial library of peptide AOMKs containing a P1 aspartic acid to probe the P2, P3, and P4 subsite specificity of endogenous legumain. Using inhibitor specificity profiles of cathepsin B and legumain, we designed fluorescent ABPs that are highly selective, cell-permeable reagents for monitoring legumain activity in complex proteomes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Cathepsin B / antagonists & inhibitors
  • Cell Membrane Permeability / physiology
  • Combinatorial Chemistry Techniques
  • Cysteine Endopeptidases / metabolism*
  • Drug Design
  • Fluorescent Dyes / chemical synthesis*
  • Fluorescent Dyes / pharmacology
  • Lysosomes / enzymology*

Substances

  • Fluorescent Dyes
  • Cysteine Endopeptidases
  • Cathepsin B
  • asparaginylendopeptidase