Self-assembled glycopeptide nanofibers as modulators of galectin-1 bioactivity.

摘要: Galectins are carbohydrate-binding proteins that act as extracellular signaling molecules in various normal and pathological processes. Galectin bioactivity is mediated by specific non-covalent interactions with cell-surface matrix (ECM) glycoproteins, which can enhance or inhibit events influence cellular behaviors, including adhesion, proliferation, differentiation, apoptosis. Here, we developed a materials approach to modulate galectin mimicking natural galectin-glycoprotein interactions. Specifically, created variant of peptide self-assembles into β-sheet nanofibers under aqueous conditions, QQKFQFQFEQQ (Q11), has an asparagine residue modified the monosaccharide N-acetylglucosamine (GlcNAc) at its N-terminus (GlcNAc-Q11). GlcNAc-Q11 self-assembled similar conditions Q11. Nanofibrillar GlcNAc moieties were efficiently converted galectin-binding disaccharide N-acetyllactosamine (LacNAc) via enzyme β-1,4-galactosyltransferase sugar donor UDP-galactose, while retaining structure nanofiber morphology. LacNAc-Q11 bound galectin-1 -3 LacNAc concentration-dependent manner, although higher affinity than galectin-3. In contrast, weakly nanofibers, no galectin-3 binding these was observed. Galectin-1 because it could be inhibited excess soluble β-lactose, carbohydrate. galectin-1-mediated apoptosis Jurkat T cells but unable activity, consistent nanofibers. We envision glycopeptide capable modulating will broadly useful biomaterials for medical applications, cancer therapeutics, immunotherapy, tissue regeneration, viral prophylaxis.