组会讲课人员:张伟
Bioorthogonal chemistry
生物正交
主讲人:张伟
Nat Rev Methods Primers|VOL 1|April 2021|30. https://doi.org/10.1038/s43586-021-00028-z
Abstract:Bioorthogonal chemistry represents a class of high-yielding chemical reactions that proceed rapidly and selectively in biological environments without side reactions towards endogenous functional groups. Rooted in the principles of physical organic chemistry, bioorthogonal reactions are intrinsically selective transformations not commonly found in biology. Key reactions include native chemical ligation and the Staudinger ligation, copper-catalysed azide–alkyne cycloaddition, strain-promoted [3 + 2] reactions, tetrazine ligation, metal-catalysed coupling reactions, oxime and hydrazone ligations as well as photoinducible bioorthogonal reactions. Bioorthogonal chemistry has significant overlap with the broader field of ‘click chemistry’ — high-yielding reactions that are wide in scope and simple to perform, as recently exemplified by sulfuryl fluoride exchange chemistry. The underlying mechanisms of these transformations and their optimal conditions are described in this Primer, followed by discussion of how bioorthogonal chemistry has become essential to the fields of biomedical imaging, medicinal chemistry, protein synthesis, polymer science, materials science and surface science. The applications of bioorthogonal chemistry are diverse and include genetic code expansion and metabolic engineering, drug target identification, antibody–drug conjugation and drug delivery. This Primer describes standards for reproducibility and data deposition, outlines how current limitations are driving new research directions and discusses new opportunities for applying bioorthogonal chemistry to emerging problems in biology and biomedicine.
摘要:生物正交化学代表一类高产化学反应,它们在生物环境中快速且有选择性地进行,不会对内源性官能团产生副反应。植根于物理有机化学的原理,生物正交反应本质上是生物学中不常见的选择性转化。关键反应包括天然化学连接和施陶丁格连接、铜催化的叠氮化物-炔烃环加成、应变促进的 [3+2] 反应、四嗪连接、金属催化的偶联反应、肟[wò]和腙连接以及光诱导生物正交反应。生物正交化学与更广泛的“点击化学”领域有显着重叠——高产反应,范围广泛且易于执行,最近以硫酰氟交换化学为例。本入门书描述了这些转变的基本机制及其最佳条件,然后讨论了生物正交化学如何成为生物医学成像、药物化学、蛋白质合成、聚合物科学、材料科学和表面科学领域必不可少的。生物正交化学的应用多种多样,包括遗传密码扩展和代谢工程、药物靶点识别、抗体-药物偶联和药物递送。本入门书描述了可重复性和数据存储的标准,概述了当前的限制如何推动新的研究方向,并讨论了将生物正交化学应用于生物学和生物医学中新出现的问题的新机会。