Impact of Glycosylation on Self-Assembled Peptide Hydrogels

Enhanced aromatic sequons (EASs) are short native sequences, often within the turn regions of proteins whose glycosylation can affect the thermodynamic stability and rates of folding and unfolding of proteins. Although much work has been done to define the biophysical underpinnings of these effects in proteins, our understanding of how glycosylation influences peptide assembly, nanostructure, and material properties remains a knowledge gap. Furthermore, the effect of glycosylation on self-assembling peptides containing naturally occurring glycosylation sites is yet to be explored. Herein, the effect of glycosylating native EASs hosted within self-assembling β-hairpin peptides is studied. Physicomechanical studies complemented by molecular dynamics simulations show that the ability of a peptide to host a properly folded glycosylated EAS is sequon-dependent, as are the resulting effects on the rates of fibril formation, nanomorphology, rates of gel network evolution, and the mechanical properties of the resultant gels. This study lays the groundwork for establishing design principles governing self-assembling glycopeptides containing native motifs for materials development.