Recently, Xi Zhen and Zhou Chuangzheng reported a new type of thiol-specific and tracelessly removable bioconjugation tools on JACS. They solved a long-term problem concerning site-specific chemical modification. Site-specific chemical modification is an invaluable approach for producing conjugated peptides and proteins, which are widely used as therapeutics and as tools for biochemical and biophysical studies. Among the 20 natural amino acids, cysteine is especially attractive for site-specific chemical modification owing to its high nucleophilicity at physiological conditions and relatively low natural abundance. Common reagents used for conjugation to cysteine include maleimides, iodoacetamides, alkyl halides, and pyridyl disulfides. In many cases, reversible modification of a target protein is desired, but reagents mentioned above cannot fulfill this function.

Xi and Zhou’s group reported that 5MPs are thiol specific, reversible bioconjugation reagents that are superior to commonly used, structurally similar maleimides. 5MPs are easy to prepare, stable under physiologically relevant conditions, and are highly thiol-specific. The conjugates formed between 5MPs and cysteines are stable at neutral pH, but tracelessly regenerate native peptides/proteins in either pH 9.5 buffer or by thiol exchange. 5MPs could be subjected to further functionalization or to generate inter/intramolecular lysine-cysteine cross-links.

Read more: http://pubs.acs.org/doi/abs/10.1021/jacs.7b00670.

This work was supported by NSFC and Natural Science Foundation of Tianjin City. C.Z. M.M.G. is grateful to the National Institute of General Medical Science for financial support.