Thiol-ene click chemistry: a biocompatible way for orthogonal bioconjugation of colloidal nanoparticles

Bioconjugation based on crosslinking primary amines to carboxylic acid groups has found broad applications in protein modification, drug development, and nanomaterial functionalization. However, proteins, which are made up of amino acids, typically give nonselective bioconjugation when using primary amine-based crosslinking. In order to control protein orientation and activity after conjugation, selective bioconjugation is desirable. We herein report an efficient and cysteine-selective thiol-ene dick reaction-based bioconjugation strategy using colloidal nanoparticles. The resulting thiol-ene based aptamer and enzyme nanoconjugates demonstrated excellent target binding ability and enzymatic activity, respectively. Thus, thiol-ene dick chemistry can provide a stable and robust crossEinker in a biocompatible manner for bioconjugation of any thiol-containing biomoIecuIe with nanomateriaIs. This will open more opportunities for applications of thiol-ene reactions and functional colloidal nanoparticles in chemical biology.