期刊
FUTURE MEDICINAL CHEMISTRY
卷 8, 期 4, 页码 381-404出版社
FUTURE SCI LTD
DOI: 10.4155/fmc-2015-0007
关键词
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For the last 15 years, kinetic target-guided syntheses, including in situ click chemistry, have been used as alternative methods to find ligands to therapeutically relevant proteins. In this review, a comprehensive survey of biological targets used in kinetic target-guided synthesis covers historical and recent examples. The chemical reactions employed and practical aspects, including controls, library sizes and product detection, are presented. A particular focus is on the reagents and warhead selection and design with a critical overview of the challenges encountered. As protein supply remains a key success factor, it appears that increased efforts should be taken toward miniaturization in order to expand the scope of this strategy and qualify it as a fully fledged drug discovery tool.
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