Self-assembled glycopeptide nanofibers as synthetic glycoprotein mimetics to modulate lectin bioactivity

摘要

Self-assembled glycopeptide nanofibers provide a simple route to create biomaterials that can modulate the activity of immunomodulatory lectins, analogous to natural ECM glycoproteins. These glycoconjugates can provide biomaterials that present sugar ligands at precisely tunable concentrations, and which can selectively bind to target lectins according to their fine-specificity for particular glycans. The reproducible self-assembly of glycopeptides into nanofibers provides a simple route to create synthetic glycoprotein mimetics that directly address challenges associated with recombinant glycoprotein expression. Increasing the sugar content of nanofibers enhances their multivalency, and in turn affinity for target lectins, effectively recapitulating the "glyco-cluster effect' provided by high carbohydrate density of natural glycoproteins. Sugar moieties are displayed along the nanofiber in such a way that they are accessible to lectin binding, as well as enzymatic treatment that can be used to precisely alter the type of sugar displayed by the nanofiber. The latter is particularly important as it will allow for a wide variety of immune-related lectin-glycoprotein interactions to be targeted by these materials. We envision that glycopeptide nanofibers that can precisely modulate natural lectin-glycoprotein interactions will provide the basis for biomaterials finding use in a broad range of immunotherapy applications.