A strain-promoted [3+2] azide-alkyne cycloaddition for covalent modification of blomolecules in living systems
A strain-promoted [3+2] azide-alkyne cycloaddition for covalent modification of blomolecules in living systems
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DOI：
10.1021/ja044996f
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发表时间：
2004-11-24
影响因子：
15
通讯作者：
Bertozzi, CR
中科院分区：
文献类型：
--
作者：
Agard, NJ;Prescher, JA;Bertozzi, CR
与生物体系的各种功能相互垂直的选择性化学反应已成为化学生物学领域的重要工具。两个值得注意的例子是叠氮化物和膦的Staudinger连接以及铜(I)催化的叠氮化物和炔烃的[3+2]环加成反应(“点击化学”)。Staudinger结扎在活体动物中具有足够的生物相容性，但存在磷化氢氧化和合成方面的挑战。点击化学消除了对膦的要求，但铜(I)催化剂对细胞有毒，从而排除了在体内的应用。在这里，我们提出了一种菌株促进的环辛炔和叠氮化物之间的[3+2]环加成反应，它在生理条件下进行，不需要催化剂。通过体外和活细胞对生物分子的选择性修饰，证明了该反应的实用性，没有明显的毒性。
Selective chemical reactions that are orthogonal to the diverse functionality of biological systems have become important tools in the field of chemical biology. Two notable examples are the Staudinger ligation of azides and phosphines and the Cu(I)-catalyzed [3 + 2] cycloaddition of azides and alkynes (“click chemistry”). The Staudinger ligation has sufficient biocompatibility for performance in living animals but suffers from phosphine oxidation and synthetic challenges. Click chemistry obviates the requirement of phosphines, but the Cu(I) catalyst is toxic to cells, thereby precluding in vivo applications. Here we present a strain-promoted [3 + 2] cycloaddition between cyclooctynes and azides that proceeds under physiological conditions without the need for a catalyst. The utility of the reaction was demonstrated by selective modification of biomolecules in vitro and on living cells, with no apparent toxicity.