Reliable and Efficient Procedures for the Conjugation of Biomolecules through Huisgen Azide-Alkyne Cycloadditions

The Cu I-catalyzed azide-alkyne cycloaddition (CuAAC) has been established as a powerful coupling technology for the conjugation of proteins, nucleic acids, and polysaccharides. Nevertheless, several shortcomings related to the presence of Cu, mainly oxidative degradation by reactive oxygen species and sample contamination by Cu, have been pointed out. This Minireview discusses key aspects found in the development of the efficient and benign functionalization of biomacromolecules through CuAAC, as well as the Cu-free strain-promoted azide-alkyne cycloaddition (SPAAC). Efficient and benign bioconjugation: Cu I-catalyzed azide-alkyne cycloaddition (CuAAC) is an established coupling method because of its high reliability and straightforward experimental procedure. However, the Cu catalyst has often proved detrimental to proteins, nucleic acids, and polysaccharides. Cu I ligands and Cu-free strain-promoted procedures (SPAAC) have been developed that are efficient and avoid degradation of the resulting bioconjugates. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.