期刊
CHEM
卷 8, 期 8, 页码 2260-2277出版社
CELL PRESS
DOI: 10.1016/j.chempr.2022.05.018
关键词
-
资金
- NIH NIEHS [1DP2ES030448]
- Claudia Adams Barr Program for Innovative Cancer Research
This article describes a chemically revertible bioconjugation strategy using enamine N-oxides for a bio-orthogonal dissociative reaction. The reaction is rapid, complete, and relatively insensitive to common buffers and pH levels. It can be paired with a bioorthogonal hydroamination reaction to create an integrated click and release system.
A chemically revertible bioconjugation strategy featuring a new bio-orthogonal dissociative reaction employing enamine N-oxides is described. The reaction is rapid, complete, directional, and traceless and displays a broad substrate scope. Reaction rates for the cleavage of fluorophores from proteins are on the order of 82 M (-1) s(-1), and the reaction is relatively insensitive to common aqueous buffers and pHs between 4 and 10. Diboron reagents with bidentate and tridentate ligands also effectively reduce the enamine N-oxide to induce dissociation and compound release. This reaction can be paired with the corresponding bioorthogonal hydroamination reaction to afford an integrated system of bioorthogonal click and release via an enamine N-oxide linchpin with a minimal footprint. The tandem associative and dissociative reactions are useful for the transient attachment of proteins and small molecules with access to a discrete, isolable intermediate. We demonstrate the effectiveness of this revertible transformation on cells by using chemically cleavable antibody- drug conjugates.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据