New organic materials are needed for anti-fouling coatings, carriers for vaccines, drug delivery, pharmaceutical, water purification, antiviral and microbial coating composites for additive manufacturing, adhesives, lubricants, and substrates mediating the biotic/abiotic interface. Many animals achieve these functions by secreting mucus, which often contains high molecular weight (M_w), heavily glycosylated proteins as a major component. Alternative efforts to create synthetic materials that mimic the structure of natural mucuses with particularly highly glycosylated peptide backbones on large scales have been hindered by substantial synthetic challenges. For example, solid-phase peptide syntheses have reproduced mucin fragments' sequence and glycan structure, but this approach is inadequate for preparing scalable high M_w polymers. Meanwhile, the post-polymerization glycosylation approach often requires non-natural linkages between the polymer and the backbone, primarily relies on synthetic backbones, and the degree of glycosylation can be difficult to control and quantify. Here, we employed the ring-opening polymerization of the N-carboxy anhydride (NCA) method to prepare synthetic mucins composed of glycosylated and cysteine containing links with polypeptide backbones. This polymerization has living characters and can achieve M_w polymers with narrow polydispersity indices, and has been adopted successfully to polymerize glycosylated NCA monomers. The polymerization of poly(β-Galactose-Threonine)-co-poly(cysteine) has been explored in different solvents, initiators, catalysts, ligands, and temperatures resulting in a tunable synthesis where β-OAc-Gal-Thr-NCA and t-butyl-cys-NCA can be varied and control to form poly(β-Gal-Thr)-co-poly(cys). The polymer properties change as it increases M_w and network, creating a mucoadhesive polymer where cross-linking cys is being explore. The development of synthetic mucins that reproduce the characteristic behaviors of their natural counterpart is attractive for meeting future soft matter needs, including adhesives that are operational in liquids, barrier coatings, biocompatible composites, herbology, and cosmetics.

Milan Shlain

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