Influence of residual chirality on the conformation and enzymatic degradation of glycopolypeptide based biomaterials

Glycopolypeptides as analogs of glycoproteins or glycosaminoglycans represent attractive building blocks for the construction of biomimetic biomaterials. However, the effects of amino acid chirality on the conformation and enzymatic degradation of glycopolypeptides are often overlooked. Here, we synthesized and characterized a range of glycopolypeptides composed of galactosylated poly(γ-propargylglutamate)s containing L- and/or D-glutamate residues. Glycopolypeptides containing pure L-glutamate residues were predominantly α-helical, and the helicity increased over the degree of polymerization of the polypeptide backbones (24 to 44). The glycopolypeptide with pure D-glutamate residues adopted a mirrored α-helical conformation, whilst apparent random coil conformation was observed for the glycopolypeptide with equally mixed enantiomeric residues. The enzymatic degradation rates of the glycopolypeptides were markedly reduced following the introduction of D-glutamate residues into backbones. Galactoside pendants on these glycopolypeptides maintained their binding to peanut agglutinin. These structure-property relationships provide new insight for the design of biomimetic biomaterials containing glycopolypeptides.