Covalent PROTAC design method based on a sulfonyl pyridone probe

文献情報

出版日 2023-11-29

DOI 10.1039/D3CC05127G

インパクトファクター 6.222

著者

Yaqi Wang, Zhanfeng Hou, Licheng Tu, Chuan Wan, Jianbo Liu, Rui Wang, Wei Han, Jianlong Wu, Fei Lu

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要旨

Covalent proteolysis-targeting chimeras (PROTACs) offer enhanced selectivity, prolonged action, and increased efficacy against challenging target proteins. The conventional approach relies on covalent ligands, but our study presents an innovative method employing an N-sulfonyl pyridone warhead to selectively target tyrosine (Tyr) residues. The von Hippel–Lindau (VHL) moiety is transferred from the warhead to the exposed Tyr, allowing us to design a STING degrader (DC50 0.53 μM, Dmax 56.65%). This approach showcases the potential of nucleophilic amino acid labeling probes, particularly for proteins lacking easily accessible cysteine residues, opening new possibilities for covalent PROTAC design and targeted protein degradation therapies.

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掲載誌

Chemical Communications

CiteScore: 8.6

自己引用率: 4.7%

年間論文数: 2458

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