赖氨酸
药物发现
化学
组合化学
半胱氨酸
共价键
电泳剂
计算生物学
生物化学
小分子
氨基酸
酶
生物
有机化学
催化作用
作者
Jonathan Pettinger,Keith Jones,Matthew D. Cheeseman
标识
DOI:10.1002/anie.201707630
摘要
Abstract Targeted covalent inhibitors have gained widespread attention in drug discovery as a validated method to circumvent acquired resistance in oncology. This strategy exploits small‐molecule/protein crystal structures to design tightly binding ligands with appropriately positioned electrophilic warheads. Whilst most focus has been on targeting binding‐site cysteine residues, targeting nucleophilic lysine residues can also represent a viable approach to irreversible inhibition. However, owing to the basicity of the ϵ ‐amino group in lysine, this strategy generates a number of specific challenges. Herein, we review the key principles for inhibitor design, give historical examples, and present recent developments that demonstrate the potential of lysine targeting for future drug discovery.
科研通智能强力驱动
Strongly Powered by AbleSci AI