Chemoselective ligation techniques enable the selective modification of proteins and other biomolecules in dilute aqueous solution. Importantly, these reactions occur at or near physiological pH and are compatible with the complex array of functional groups commonly found in biological macromolecules including proteins, nucleotides, and carbohydrates, allowing conjugation reactions to be carried out on unprotected substrates. Recently, a growing number of reactions with established utility in synthetic organic chemistry have been shown to have surprising utility in the context of biological molecules in aqueous media. In this review we highlight several promising reactions that may have widespread applicability in the generation of new materials based on biological macromolecules.
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