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

doi:10.1016/j.bmcl.2006.10.100

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 journal › Article › peer-review

44 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 language	English
Pages (from-to)	649-653
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	17
Issue number	3
DOIs	https://doi.org/10.1016/j.bmcl.2006.10.100
State	Published - 1 Feb 2007
Externally published	Yes

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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10.1016/j.bmcl.2006.10.100

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AU - Bogyo, Matthew

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

Abstract

Bibliographical note

Keywords

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