New Cysteine Covalent Modification Strategies Enable Advancement of Proteome‐wide Selectivity of Kinase Modulators
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- Ivy Guan
- School of Chemistry The Heart Research Institute The University of Sydney Sydney New South Wales 2006 Australia
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- Kayla Williams
- School of Chemistry The University of Sydney Sydney New South Wales 2006 Australia
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- Jolyn Pan
- Faculty of Science & Engineering The University of Waikato 124 Hillcrest Road, Hillcrest Hamilton 3216 New Zealand
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- Xuyu Liu
- School of Chemistry The Heart Research Institute The University of Sydney Sydney New South Wales 2006 Australia
Description
<jats:title>Abstract</jats:title><jats:p>There has been tremendous progress in covalent inhibitors as evidenced by the ascent of innovative electrophilic warheads with suppressed non‐specific reactivity but enhanced capacity for proximity‐driven covalent reactions with nucleophilic residues in the targeted site. Kinases, a central player in cancers, autoimmune disorders and chronic diseases, represent a highly targeted class of enzymes by covalent inhibitors. However, innovative strategies to afford high selectivity in target recognition remain a pressing need. This minireview focuses on four promising strategies to achieve superior target selectivity through rational design of the covalent engagement. Special emphasis is placed on examples where the selectivity had arisen by complementing the reactivity of protein cysteines with electrophilic warheads specified for distinct covalent chemistry, or inspired from native electrophile signalling in cells.</jats:p>
Journal
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- Asian Journal of Organic Chemistry
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Asian Journal of Organic Chemistry 10 (5), 949-963, 2021-04-14
Wiley
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Keywords
Details 詳細情報について
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- CRID
- 1360861709485937152
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- ISSN
- 21935815
- 21935807
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- Data Source
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- Crossref