Publication
Title
Pepstatin-based probes for photoaffinity labeling of aspartic proteases and application to target identification
Author
Abstract
Aspartic proteases are a small class of proteases implicated in a wide variety of human diseases. Covalent chemical probes for photoaffinity labeling (PAL) of these proteases are underdeveloped. We here report a full on-resin synthesis of clickable PAL probes based on the natural product inhibitor pepstatin incorporating a minimal diazirine reactive group. The position of this group in the inhibitor determines the labeling efficiency. The most effective probes sensitively detect cathepsin D, a biomarker for breast cancer, in cell lysates. Moreover, through chemical proteomics experiments and deep learning algorithms, we identified sequestosome-1, an important player in autophagy, as a direct interaction partner and substrate of cathepsin D.
Language
English
Source (journal)
ACS Chemical Biology. - -
Publication
2023
ISSN
1554-8929
DOI
10.1021/ACSCHEMBIO.2C00946
Volume/pages
18 :4 (2023) , p. 686-692
ISI
001059104900001
Pubmed ID
36920024
Full text (Publisher's DOI)
Full text (publisher's version - intranet only)
UAntwerpen
Faculty/Department
Research group
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identifier
Creation 02.10.2023
Last edited 03.11.2024
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