Chemistry in living systems

Abstract

Dissecting complex cellular processes requires the ability to track biomolecules as they function within their native habitat. Although genetically encoded tags such as GFP are widely used to monitor discrete proteins, they can cause significant perturbations to a protein's structure and have no direct extension to other classes of biomolecules such as glycans, lipids, nucleic acids and secondary metabolites. In recent years, an alternative tool for tagging biomolecules has emerged from the chemical biology community--the bioorthogonal chemical reporter. In a prototypical experiment, a unique chemical motif, often as small as a single functional group, is incorporated into the target biomolecule using the cell's own biosynthetic machinery. The chemical reporter is then covalently modified in a highly selective fashion with an exogenously delivered probe. This review highlights the development of bioorthogonal chemical reporters and reactions and their application in living systems.

Bioorthogonal Catalytic Activation of Platinum and Ruthenium Anticancer Complexes by FAD and Flavoproteins

“…The latest advances in bioorthogonal chemistry1 demonstrate how organometallic compounds and inorganic materials are capable of catalyzing the activation of profluorescent substrates and prodrugs with remarkable efficiency in biological environments 2, 3, 4, 5, 6, 7, 8, 9, 10. These selective catalysts carry out non‐natural reactions dodging the interference of biological molecules, in some cases with endogenous cellular components as co‐reactants 3, 9…”

Nucleophilic Catalysis of Oxime Ligation

“…Furthermore, aniline is soluble in a range of solvents and can be used as a convenient aqueous buffer with acetic acid, and both its solubility and nucleophilicity can be tuned through the introduction of substituents on the aromatic ring. Aniline catalysis will have a major impact on the numerous applications of imine chemistry including bioconjugation, [1][2][3][4][5][6][7][8] cellular labeling, [18,19] surface immobilization, [20] and dynamic combinatorial libraries. [21,22] .…”

Copper-free click chemistry for dynamic in vivo imaging

“…In this approach, the cell's metabolic machinery is used to install a bioorthogonal functional group into target biomolecules, which is then covalently labeled in a second step with a probe (5). The azide is the most widely used chemical reporter because of its small size, metabolic stability, and lack of reactivity with natural biofunctionality.…”

“…The azide is the most widely used chemical reporter because of its small size, metabolic stability, and lack of reactivity with natural biofunctionality. Azides have been introduced into glycans, lipids, and proteins in living cells (5), and in the case of glycans in living animals (6), with minimal physiological perturbation.…”