Ultra-rapid Electrophilic Cysteine Arylation.
Ultra-rapid Electrophilic Cysteine Arylation.
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DOI：
10.1021/jacs.3c10334
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发表时间：
2023-10
影响因子：
15
通讯作者：
Bradley M Lipka;Daniel S Honeycutt;Gregory M Bassett;Taylor N Kowal;Max Adamczyk;Zachary C Cartnick;V. Betti;Jacob M. Goldberg;Fang Wang
中科院分区：
文献类型：
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作者：
Bradley M Lipka;Daniel S Honeycutt;Gregory M Bassett;Taylor N Kowal;Max Adamczyk;Zachary C Cartnick;V. Betti;Jacob M. Goldberg;Fang Wang
快速成键反应是高效生物偶联的关键。我们描述了一种简单实用的策略来促进超快速亲电半胱氨酸芳基化。使用多种磺胺活化的吡啶盐，在pH 7.0的水溶液缓冲液中，在25°C下，以非常高的速率常数进行非催化反应，速率常数从9800到320,000 M-1·s-1不等。这样的反应允许在几分钟甚至几秒钟内进行微摩尔半胱氨酸的化学计量生物偶联。尽管芳基化非常快，但化学反应表现出优异的选择性，从而提供了高转化率和高纯度的功能化肽和蛋白质。
Rapid bond-forming reactions are crucial for efficient bioconjugation. We describe a simple and practical strategy for facilitating ultra-rapid electrophilic cysteine arylation. Using a variety of sulfone-activated pyridinium salts, this uncatalyzed reaction proceeds with exceptionally high rate constants, ranging from 9800 to 320,000 M-1·s-1, in pH 7.0 aqueous buffer at 25 °C. Such reactions allow for stoichiometric bioconjugation of micromolar cysteine within minutes or even seconds. Even though the arylation is extremely fast, the chemistry exhibits excellent selectivity, thus furnishing functionalized peptides and proteins with both high conversion and purity.