Bioorthogonal Chemistry: Fishing for Selectivity in a Sea of Functionality

Abstract

The study of biomolecules in their native environments is a challenging task because of the vast complexity of cellular systems. Technologies developed in the last few years for the selective modification of biological species in living systems have yielded new insights into cellular processes. Key to these new techniques are bioorthogonal chemical reactions, whose components must react rapidly and selectively with each other under physiological conditions in the presence of the plethora of functionality necessary to sustain life. Herein we describe the bioorthogonal chemical reactions developed to date and how they can be used to study biomolecules.

Covalent Cell Surface Functionalization of Human Fetal Osteoblasts for Tissue Engineering

“…[1][2][3][4][5] The chemical motifs involved in these reactions include peptide sequence with specific side chain combinations, carbonyl moieties for condensation with aminooxy or hydrazides probes, and azides for Staudinger ligation with triarylphosphines and cycloadditions to alkynes. 6,7 The biocompatibility of these reactions provides efficient tools for the modification of proteins, the labeling of enzymes, the metabolic labeling of cell-surface glycans and lipids within their native cellular environment and thus allows to study the biological processes in which these biomolecules are involved.…”

Selective chemical protein modification

“…Potential transformations, if they are to be relevant, are moulded by the need for biologically ambient conditions (that is, o37°C, pH 6-8, aqueous solvent) so as not to disrupt protein architecture and/or function. Ideally, this should proceed with near total conversion to generate homogenous constructs [2][3][4] . The applications of modified proteins are many; they are as varied as the in vivo tracking of protein-fluorophore conjugates 5 to the polyethylene glycol (PEG)ylation of therapeutic proteins to reduce immunogenicity 6 , from the production of materials with novel properties 7 to probing the mechanism of pathological enzymes 8 .…”

Dual Strain-Promoted Alkyne–Nitrone Cycloadditions for Simultaneous Labeling of Bacterial Peptidoglycans

“…1 This two-step process typically involves metabolic or enzymatic incorporation of a bioinert functional group, followed by subsequent detection through covalent attachment of a reporter tag bearing the paired functional group. 2 One of the most well-characterized bioorthogonal reactions is the copper-catalyzed azide−alkyne cycloaddition (CuAAC).…”