Bioorthogonal click chemistry: Covalent labeling in living systems

The term click chemistry defines a powerful set of chemical reactions that are rapid, selective, and high-yielding. These reactions, some of which are less than 10 years old, have been applied in diverse areas, including drug discovery, materials science, and chemical biology. In chemical biology, click chemistry has been used in the selective labeling of biomolecules within living systems, allowing proteins, glycans, and other important biomolecules to be monitored in a physiologically relevant environment rather than in an in vitro setting. This demanding application requires not only the aforementioned characteristics of click chemistry but, additionally, that the reactions are bioorthogonal - that is, non-interacting with biological functionality while proceeding under physiological conditions - and that the reagents are non-toxic. Of the many extant click reactions, only a select few possess this unique combination of attributes, notably the Staudinger ligation of azides and triarylphosphines and [3+2] dipolar cycloadditions of azides with strained alkynes. This minireview describes the characteristics of bioorthogonal click reactions as well as recent applications toward labeling biomolecules in cells and living organisms.