Sulfonium alkylation followed by ‘click’ chemistry for facile surface modification of proteins and tobacco mosaic virus

Alkylsulfonium salts (ASS) have been shown to act as powerful alkylating agents. However, few studies have addressed the application of sulfonium salts to the modification of biomolecules such as nucleic acids and proteins. Since these large biomolecules play important roles in biological processes, a convenient and fast method for their modification is greatly needed. In this work, for the first time, we used a tandem method of sulfonium alkylation and click chemistry (CuAAC) for modification of biomolecules. Fluorescent labeling of proteins and tobacco mosaic virus were successfully performed after simple incubation of biomolecules with sulfonium salts followed by azido-containing compound at room temperature. This facile bioconjugation assay based on ASS-CuAAC reactions should be useful in protein chemistry and bionanoscience.