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Updated: Oct 24, 2025

Synthesis and Bioconjugation of Thiol-Reactive Reagents for the Creation of Site-Selectively Modified Immunoconjugates
Published on: March 6, 2019
An Ionic Liquid Medium Enables Development of a Phosphine-Mediated Amine-Azide Bioconjugation Method
Hisham M El-Shaffey1, Elizabeth J Gross1, Yvonne D Hall1
1Department of Chemistry, North Carolina State University, Raleigh, North Carolina 27695, United States.
Abstract:
While a diverse set of design strategies have produced various chemical tools for biomolecule labeling in aqueous media, the development of nonaqueous, biomolecule-compatible media for bioconjugation has significantly lagged behind. In this report, we demonstrate that an aprotic ionic liquid serves as a novel reaction solvent for protein bioconjugation without noticeable loss of the biomolecule functions. The ionic liquid bioconjugation approach led to discovery of a novel triphenylphosphine-mediated amine-azide coupling reaction that forges a stable tetrazene linkage on unprotected peptides and proteins. This strategy of using untraditional media would provide untapped opportunities for expanding the scope of chemical approaches for bioconjugation.
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