Unnatural biopolymers of saccharides and proteins conjugated with poly(2-oxazoline) and methacrylate-based polymers: from polymer design to bioapplication

• Published in: Polymer journal 2022-12, Vol.54 (12), p.1431-1444
• Main Author: Koda, Yuta
• Format: Article
• Language: English
• Subjects: 140/131; 639/301/54/989; 639/638/455/941; Addition polymerization; Biomaterials; Bioorganic Chemistry; Biopolymers; Carbohydrates; Cationic polymerization; Chains (polymeric); Chemistry; Chemistry and Materials Science; Chemistry/Food Science; Chymotrypsin; Conjugation; Copolymers; Decomposition reactions; Enzymes; Focus Review; Folding; Glycopolymers; Lysozyme; Monomers; Nanoparticles; Oligosaccharides; Polyethylene glycol; Polymer Sciences; Polymerization; Polymers; Polyoxazolines; Proteins; Ring opening polymerization; Stabilization; Surfaces and Interfaces; Thin Films
• ISSN: 0032-3896; 1349-0540
• DOI: 10.1038/s41428-022-00695-z

In this focus review, recent developments in unnatural sugar- and protein-based polymers and their future bioapplications are discussed. A new unnatural oligoaminosaccharide carrying N -1,2-glycosidic bonds that cannot be prepared in natural biological systems has been proposed. To prepare the oligomers, a sugar monomer possessing a 2-methyl-2-oxazoline (MeOx) ring was polymerized via cationic ring-opening polymerization. This polymerization did not proceed by the classical MeOx mechanism but by a new mechanism involving sequential S N 1-type reactions. This unnatural oligosaccharide was not decomposed by the natural enzymes owing to the unnatural N -1,2-glycosidic bonds, indicating promise in applications as a new class of glycomaterials. Furthermore, technology for stabilizing proteins using protein–polymer conjugations and polymer chain-folding nanoparticles has recently been developed. Amphiphilic/fluorous methacrylate-based random copolymers bearing polyethylene glycol (PEG) and fluorous side chains formed reversible PEG and fluorous compartments in water and 2 H ,3 H -perfluoropentane (2HPFP), respectively. These copolymers were noncytotoxic and successfully conjugated with lysozymes. They also stabilized lysozyme and α -chymotrypsin in 2HPFP, and the enzymes were not denatured after extraction from 2HPFP. This focus review discussed our recent developments of unnatural glycopolymers based on polyoxazoline, protein–polymer conjugates, and protein stabilization. To develop new glycopolymers, a bicyclic monomer composed of glucosamine and 2-methyl-2-oxazoline (MeOx) was designed. This cationic ring-opening polymerization proceeded not by the mechanism for MeOx but by a new polymerization mechanism. This oligosaccharide has promise to be applied to a new glycomaterial owing to the polymer design. Additionally, protein conjugation and encapsulation by amphiphilic/fluorous chain-folding nanoparticles were investigated. Fluorous nature in random copolymers was useful for the protein conjugation and stabilization.