bioRxivJClub
Electrophilic Multi-Kinase Probes Identify Degradation and Aspartate Conjugation of ULK1
bioRxiv · · Preprint · Open access
Kocaturk, Pinto + 7 more
Abstract ↗AI summary
The abstract is read at the publisher; the summary is JClub's.
ALP-1, a targeted monovalent ULK1 degrader chemical tool, controls ULK1 abundance and engages ULK1 via an atypical chloroacetamide–aspartate conjugation at the ATP-binding site.
- Why it matters: Classical reversible kinase inhibitors may not achieve the specificity or modulation needed across disease areas, motivating workflows that probe how minimal electrophilic changes alter kinase function in cells.
- What they did: The authors built a systematic workflow using minimal electrophilic modifications to ATP-site binding scaffolds, then performed scaffold-hopping to generate ALP-1 and investigated its ULK1 engagement mechanism.
- The result: The study shows chloroacetamide warheads can undergo non-cysteine reactivity through aspartate conjugation, enabling new strategies for covalent engagement and monovalent kinase degradation.
The findingWhy it mattersWhat they didThe result
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