Applications of the Cu-Catalyzed Azide-Alkyne Cycloaddition CuAAC in Peptides

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

Click Reactions in Organic Synthesis, First Edition. Edited by Srinivasan Chandrasekaran. 

A particularly relevant class of biomolecules comprises the so-called glycoproteins or glycopeptides. As with protein-protein (such as RGD-integrin) interactions, the interactions between carbohydrates and proteins facilitate many important biological processes [11, 12). Monovalent carbohydrate-protein interactions show very weak binding affinities (Kj 10 to 10 M) [7], while multivalent interactions frequently enhance the affinity due to the so-called g/y-coside cluster effects [13,14]. In order to study multivalent carbohydrate-protein interactions, multivalent glycoclusters are required. Polymers, dendrimers, benzene scaffolds, monosaccharides, and others can be used as the base to affix multiple carbohydrate units. Chen et al. [15] chose the cyclic decapeptide cyclo-[GPKAKGPKKK] where the Lys 3, 5, 8, and 10 residues were used for functionalization with propiolic acid to yield the tetravalent alkyne 8a, while 

The fact that the triazole is a bioisostere of the amide bond was also shown by the chemoenzymatic process that was used to couple the oligosaccharide to the 

18b were then coupled successfully, fulfilling the time constraint in excellent yield. 

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