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Title
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Pepstatin-based probes for photoaffinity labeling of aspartic proteases and application to target identification
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Author
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Abstract
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| 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. |
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Language
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English
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Source (journal)
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ACS Chemical Biology. - -
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Publication
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2023
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ISSN
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1554-8929
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DOI
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10.1021/ACSCHEMBIO.2C00946
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Volume/pages
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18
:4
(2023)
, p. 686-692
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ISI
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001059104900001
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Pubmed ID
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36920024
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Full text (Publisher's DOI)
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Full text (publisher's version - intranet only)
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