Tuning carbohydrate density enhances protein binding and inhibition by glycosylated β-sheet peptide nanofibers. (30th July 2018)

• Record Type: Journal Article
• Authors: Restuccia, Antonietta; Hudalla, Gregory A.
• Is Part Of: Biomaterials science. Volume 6:Number 9(2018)
• Page Start: 2327
• Page End: 2335
• Publication Date: 2018-07-30
• Subjects: Biomedical materials -- Periodicals; 610.28
• DOI: 10.1039/c8bm00533h
• Languages: English
• ISSNs: 2047-4830

Abstract

Abstract : The efficacy of glycosylated β-sheet peptide nanofibers for inhibiting carbohydrate-binding proteins can be increased by tuning carbohydrate density to maximize protein binding affinity. Abstract : Carbohydrate-modified biomaterials are attractive candidates for disrupting natural protein–glycan binding events because they present ligands in multivalent arrangements that can address the weak affinity of monovalent protein–carbohydrate interactions. However, protein binding depends on physical aspects of immobilized carbohydrate display, such as density and valency, which are often difficult to predict and can vary for different types of biomaterials. Here, we report on protein interactions with β-sheet peptide nanofibers with tunable immobilized carbohydrate content, which were prepared by co-assembling QQKFQFQFEQQ (Q11) with a glycosylated variant modified with N -acetylglucosamine (GQ11) at different molar ratios. The rate of protein binding increased as carbohydrate density decreased, with nanofibers having a GQ11 : Q11 molar ratio of 1 : 3 reaching equilibrium faster than formulations with a GQ11 mole fraction of 1. Larger proteins demonstrated a lower extent of binding than smaller proteins; however, the optimal range of carbohydrate densities was independent of the protein size. Nanofibers with the highest apparent protein binding affinity inhibited T cell death induced by wheat germ agglutinin (WGA) more effectively than did sub-optimal formulations, because they bound more protein within biologically relevant time frames (min to h). Collectively, these observations suggest that tuning carbohydrate density via co-assembly of glycosylated and non-glycosylated Q11 variants can maximize multivalent avidity effects while minimizing steric penalties. We anticipate that this approach will enable rapid iterative development of biomaterials with optimal activity for inhibiting the protein–glycan interactions implicated in disease progression.