Site-Selective Cysteine-Cyclooctyne Conjugation

被引：79

作者：

Zhang, Chi ^{[1
]}

Dai, Peng ^{[1
]}

Vinogradov, Alexander A. ^{[1
]}

Gates, Zachary P. ^{[1
]}

Pentelute, Bradley L. ^{[1
]}

机构：

[1] MIT, Dept Chem, 77 Massachusetts Ave, Cambridge, MA 02139 USA

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2018年 / 57卷 / 22期

关键词：

bioconjugation; bioorthogonal chemistry; cysteine-cyclooctyne reaction; dibenzocyclooctyne; protein modification; AZIDE-ALKYNE CYCLOADDITION; IN-VITRO; CHEMISTRY; PEPTIDES; SPECIFICITY; PROTEASES; PROTEINS; MOTIFS; SYSTEM; CELLS;

D O I：

10.1002/anie.201800860

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

We report a site-selective cysteine cyclooctyne conjugation reaction between a seven-residue peptide tag (DBCO-tag, Leu-Cys-Tyr-Pro-Trp-Val-Tyr) at the N or C terminus of a peptide or protein and various aza-dibenzocy-clooctyne (DBCO) reagents. Compared to a cysteine peptide control, the DBCO-tag increases the rate of the thiolyne reaction 220-fold, thereby enabling selective conjugation of DBCO-tag to DBCO-linked fluorescent probes, affinity tags, and cytotoxic drug molecules. Fusion of DBCO-tag with the protein of interest enables regioselective cysteine modification on proteins that contain multiple endogenous cysteines; these examples include green fluorescent protein and the antibody trastuzumab. This study demonsiraies that short peptide tags can aid in accelerating bond-forming, reactions that are often slow to non-existentin water.

引用

页码：6459 / 6463

页数：5

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