In Vivo Applications of Bioorthogonal Chemistries

Abstract

This chapter reviews the development and optimization of four bioorthogonal reactions: the Staudinger ligation, copper-catalyzed azide-alkyne cycloaddition, copper-free click chemistry, and the tetrazine ligation. It highlights the efforts of researchers to enhance the pharmacokinetic properties of bioorthogonal reagents, thereby enabling their use in vivo and opening the door to exciting new applications of these unique chemistries. In order for a bioorthogonal reaction to be successful in vivo, one of the reaction partners must be somehow integrated into the target biomolecule. The chapter presents examples in which metabolic glycan engineering is used to install reactive bioorthogonal handles into the glycomes of living animals. Most of the in vivo metabolic labeling experiments presented in the chapter employ peracetylated versions of the sugar analogs, which readily penetrate cell membranes and are deacetylated by cytosolic esterases.