Applications of the Cu ‐Catalyzed Azide–Alkyne Cycloaddition ( CuAAC ) in Peptides

This chapter focuses on applications of the Cu-Catalyzed Azide-Alkyne Cycloaddition (CuAAC) reaction in combination with peptides and proteins. It highlights approaches in which the click reaction has been used as a tool to conjugate peptides, containing either an azide or an alkyne functional handle on one of the side chains or at one of the termini, with molecules in the broadest sense containing the complementary functional group. The chapter describes examples of peptides in which the backbone has been modified by incorporating a triazole instead of an amide functional group, where the properties of the resulting peptidomimetics have been evaluated. The most common application of the Huisgen click reaction in peptides is the conjugation with tags or labels, for example, detection or activity-based protein profiling. Conjugation of peptides with poly(ethylene glycol) (PEG) will give rise to the so-called PEGylated peptides, which often display higher in vivo stability and longer circulation times than their non-PEGylated counterparts.