Evaluation of self-assembled glycopeptide nanofibers modified with N,N'-diacetyllactosamine for selective galectin-3 recognition and inhibition

The carbohydrate-binding protein galectin-3 (Gal3) is an attractive drug target due to its role as a modulator of cell behavior in various pathological processes. However, development of effective Gal3 inhibitors has been hindered by the conserved binding properties of different galectins and the low affinity of monovalent protein–carbohydrate interactions. Immobilizing carbohydrates onto biomaterials can enhance their effectiveness for inhibiting galectins by establishing multivalent avidity effects that increase their apparent galectin-binding affinity. Here, we evaluated a candidate multivalent Gal3 inhibitor based on self-assembled peptide nanofibers modified with N,N′-diacetyllactosamine (i.e., “LacDiNAc”), a disaccharide that preferentially binds Gal3. QQKFQFQFEQQ (“Q11”) nanofibers modified with LacDiNAc (i.e., “LacDiNAc-Q11”) bound Gal3 with micromolar affinity and selectively captured Gal3 in the presence of galectin-1. However, LacDiNAc-Q11 nanofibers failed to inhibit Jurkat T cell death induce...