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

Kelly B. Sexton, Martin D. Witte, Galia Blum, Matthew Bogyo*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

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.

Original languageAmerican English
Pages (from-to)649-653
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume17
Issue number3
DOIs
StatePublished - 1 Feb 2007
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by an NIH National Technology Center for Networks and Pathways grant U54 RR020843 (to M.B.), NIH Grant R01-EB005011 (to M.B.), a Department of Defense Breast Cancer Center of Excellence Grant DAMD-17-02-0693 (to M.B.), and a Susan G. Koman post-doctoral fellowship (to K.B.S.).

Keywords

  • Activity-based probes
  • Cysteine protease
  • Fluorescent labeling
  • Legumain

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