Click Chemistry for Peptidomimetic Applications

1,2,3-Triazoles are popular components of peptidomimetics, i.e. compounds that mimic the structure and function of peptides. This is due to their easy access via click chemistry, as well as their dipolar properties and hydrogen bonding capacities, allowing them to act as isosteres for a cis or trans amide bond depending on their substitution pattern. In this chapter, we provide an overview of the use of copper- and ruthenium-catalysed azide-alkyne cycloadditions in the context of peptidomimetics in the last 10 years. Focus is on both linear and macrocyclic derivatives, as well as the use of triazoles as disulfide bond mimetics and for stapling purposes. Peptidotriazolamers, i.e. synthetic triazole oligomers studied for their conformational and folding properties, are also described.