Work

Site‐Selective Cysteine–Cyclooctyne Conjugation

Year: 2018

Type: article

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.

Source: Angewandte Chemie International Edition

DOI: 10.1002/anie.201800860

Authors: Chi Zhang, Peng Dai, Alexander A. Vinogradov, Zachary P. Gates, Bradley L. Pentelute

Institution: Massachusetts Institute of Technology

Language: English

Topic: Click Chemistry and Applications

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: green

Funders: Defense Advanced Research Projects Agency, National Institute of General Medical Sciences

Awards: G652502287, G7988586476, Cysteine Arylation