Associate professor Jiang Xia, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China

Site-specific Bioconjugation Reactions: The Chemistry and Biological Applications

Intrigued by the bind-then-bond mechanism of enzymatic reactions, and that of covalent drugs that have significantly impacted our human kind, we devised a set of site-specific covalent reactions between non-enzymatic proteins and reactive peptides, specifically targeting cysteine, or tyrosine, or lysine residues on the protein. These reactions were found to be spontaneous, rapid, and amenable to intracellular cytosolic conditions. These reactions have been validated in a set of biological applications. First, covalent labeling of cell surface proteins using the tag and targeted reactive peptides was manifested. Second, the reactive peptides can effective block protein-protein interaction inside cells, and thereby redirect signal transduction effectively. In particular, utilizing such a targeted covalent peptide, we elucidated a neuronal guidance pathway with unprecedented details. Moreover, the bioconjugation reactions have found use in covalent assembly of multienzyme complexes and expedited the biosynthesis of valuable terpene natural products. Besides, the targeted reactive peptides can serve as “infinite-affinity antibodies” to effectively pull down the protein of interest for proteomic studies. Taken together, new advances in site-specific bioconjugation techniques have open the door to vast possibilities that will lead to new discoveries in biology.

Host: Associate professor Menglin Chen, iNANO & Department of Engineering, Aarhus University