CATCH(+/−) peptide co-assemblies form injectable, biocompatible hydrogels with sequence-dependent viscoelastic properties.

Carbohydrate-modified peptides (i.e., “glycopeptides”) inspired by natural glycoproteins and proteoglycans are receiving increasing interest as the basis for biomaterials with advanced structural and functional properties. This chapter first introduces the reader to different chemical and enzymatic methods that are used to synthesize glycosylated peptides. Then, the chapter presents examples in which the structure of peptides and peptide-based materials can be varied through glycosylation. Finally, the chapter highlights the emerging use of glycosylated peptide materials for medical and biotechnology applications, including protein recognition, cell scaffolding, drug delivery, vaccines, and disease treatment. Collectively, the examples surveyed in this chapter demonstrate the enormous potential of carbohydrate conjugates to inform the structure of peptide-based biomaterials, as well as to endow them with new functional capabilities.

Owing to their biocompatibility and biodegradability, short synthetic peptides that self-assemble into elongated β-sheet fibers (i.e., peptide nanofibers) are widely used to create biomaterials for diverse medical and biotechnology applications. Glycosylation, which is a common protein post-translational modification, is gaining interest for creating peptide nanofibers that can mimic the function of natural carbohydrate-modified proteins. Recent reports have shown that glycosylation can disrupt the fibrillization of natural amyloid-forming peptides. Here, using transmission electron microscopy, fluorescence microscopy, and thioflavin T spectroscopy, we show that glycosylation at a site external to the fibrillization domain can alter the self-assembly pathway of a synthetic fibrillizing peptide, NSGSGQQK­FQFQFEQQ (NQ11). Specifically, an NQ11 variant modified with N-linked N-acetylglucosamine, N­(GlcNAc)­SGSG-Q11 (GQ11), formed β-sheet nanofibers more slowly than NQ11 in deionized water (pH 5.8), which correlated to the tendency of GQ11 to form a combination of short fibrils and nonfibrillar aggregates, whereas NQ11 formed extended nanofibers. Acidic phosphate buffer slowed the rate of GQ11 fibrillization and altered the morphology of the structures formed yet had no effect on NQ11 fibrillization rate or morphology. The buffer ionic strength had no effect on the fibrillization rate of either peptide, while the diphosphate anion had a similar effect on the rate of fibrillization of both peptides. Collectively, these data demonstrate that a glycan moiety located external to the β-sheet fibrillizing domain can alter the pH-dependent self-assembly pathway of a synthetic peptide, leading to significant changes in the fibril mass and morphology of the structures formed. These observations add to the understanding of the effect of glycosylation on peptide self-assembly and should guide future efforts to develop biomaterials from synthetic β-sheet fibrillizing glycopeptides.