Site-Selective Cysteine-Cyclooctyne Conjugation
Name
nihms-988725.pdf
Description
Accepted version
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967.6 KB
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Author(s)
Zhang, Chi
Dai, Peng
Vinogradov, Alexander A.
Gates, Zachary P
Pentelute, Bradley L.
Date Issued
March 2018
Journal
Angewandte Chemie International Edition
Publisher
Wiley
Citation
Zhang, Chi et al. "Site-Selective Cysteine-Cyclooctyne Conjugation." Angewandte Chemie International Edition 57, 22 (May 28, 2018): 6459-6463 © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Version
Author's final manuscript
Abstract
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-dibenzocyclooctyne (DBCO) reagents. Compared to a cysteine peptide control, the DBCO-tag increases the rate of the thiol–yne 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 demonstrates that short peptide tags can aid in accelerating bond-forming reactions that are often slow to non-existent in water. Keywords: bioconjugation; bioorthogonal chemistry; cysteine–cyclooctyne reaction; dibenzocyclooctyne, protein modification
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
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DOI of Published Version
https://doi.org/10.1002/anie.201800860
