A comparison of triazole-forming bioconjugation techniques for constructing comb-shaped peptide-polymer bioconjugates

The grafting-to of a peptide to a side chain functional polymer was investigated using "click" chemistry. Two click reactions were compared: the copper-free strain-promoted azide-alkyne 1,3-cycloaddition (SPAAC) and the traditional copper-catalyzed azide-alkyne 1,3-cycloaddition (CuAAC). For the resulting comb-shaped products, it was found that the steric bulk of the conjugation moiety used in SPAAC limits the degree of grafting for these highly dense systems, whereas CuAAC gives (near) quantitative functionalization. The SPAAC and CuAAC "click" reactions are compared in the construction of comb-shaped peptide-polymer bioconjugates. It is shown that the CuAAC gives higher grafting densities, while the steric bulk of the conjugation moiety used in SPAAC seems to limit the degree of functionalization.