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The term bioorthogonal chemistry refers to any chemical reaction that can occur inside of living systems without interfering with native biochemical processes. The term was coined by Carolyn R. Bertozzi in 2003. Since its introduction, the concept of the bioorthogonal reaction has enabled the study of biomolecules such as glycans, proteins, and lipids in real time in living systems without cellular toxicity. A number of chemical ligation strategies have been developed that fulfill the requirements of bioorthogonality, including the 1,3-dipolar cycloaddition between azides and cyclooctynes (also termed copper-free click chemistry), between nitrones and cyclooctynes, oxime/hydrazone formation from aldehydes and ketones, the tetrazine ligation, the isocyanide-based click reaction, and most recently, the quadricyclane ligation. The use of bioorthogonal chemistry typically proceeds in two steps. First, a cellular substrate is modified with a bioorthogonal functional group (chemical reporter) and introduced to the cell; substrates include metabolites, enzyme inhibitors, etc. The chemical reporter must not alter the structure of the substrate dramatically to avoid affecting its bioactivity. Secondly, a probe containing the complementary functional group is introduced to react and label the substrate. Although effective bioorthogonal reactions such as copper-free click chemistry have been developed, development of new reactions continues to generate orthogonal methods for labeling to allow multiple methods of labeling to be used in the same biosystems. ==Requirements for Bioorthogonality== To be considered bioorthogonal, a reaction must fulfill a number of requirements: * Selectivity: The reaction must be selective between endogenous functional groups to avoid side reactions with biological compounds * Biological Inertness: Reactive partners and resulting linkage should not possess any mode of reactivity capable of disrupting the native chemical functionality of the organism under study. * Chemical Inertness: The covalent link should be strong and inert to biological reactions. * Kinetics: The reaction must be rapid so that covalent ligation is achieved prior to probe metabolism and clearance. The reaction must be fast, on the time scale of cellular processes (minutes) to prevent competition in reactions which may diminish the small signals of less abundant species. Rapid reactions also offer a fast response, necessary in order to accurately track dynamic processes. * Reaction Biocompatibility: Reactions have to be non-toxic and must function in biological conditions taking into account pH, aqueous environments, and temperature. Pharmacokinetics are a growing concern as bioorthogonal chemistry expands to live animal models. * Accessible Engineering: The chemical reporter must be capable of incorporation into biomolecules via some form of metabolic or protein engineering. Optimally, one of the functional groups is also very small so that it does not disturb native behavior. 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「bioorthogonal chemistry」の詳細全文を読む スポンサード リンク
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