What is bioorthogonal chemistry?

Bioorthogonal chemistry is a class of chemical reactions that can occur inside of living systems without interfering with native biochemical processes. A few requirements must be fulfilled for a reaction to be considered bioorthogonal, such as high selectivity, fast kinetics, biological and chemical inertness, biocompatibility as well as accessibility for engineering.

Bioorthogonal reactions are commonly used in bioconjugation, which typically proceed in two steps. First, a cellular substrate, such as metabolites and enzyme inhibitors, is modified with a functional group and introduced to the cell. The functional group must have minimal alteration to the structure of the substrate to avoid affecting its bioactivity. Secondly, a probe containing the complementary functional group is introduced to react and label the substrate. Since the functional group installed on the substrate is unique and non-native, the bioconjugation process using bioorthogonal reactions can be more selective and controllable than the traditional ones involving native amino acid residues.