Facile synthesis of polymethionine oxides through polycondensation of activated urethane derivative of α-amino acid and their application to antifouling polymer against proteins and cells

Abstract

We have developed a facile route for the synthesis of poly(methionine) and poly(methionine oxide), including poly(methionine sulfoxide), and poly(methionine sulfone) through polycondensation of the corresponding N-phenoxycarbonyl derivatives of α-amino acids in the presence of amines. These urethane derivatives were readily synthesized through N-carbamylation of onium salt of methionine with diphenyl carbonate. Oxidation of sulfide on the urethane derivative with a hydrogen peroxide selectively provided the corresponding sulfoxide and sulfone in high yield. Heating of their urethane derivative 60 °C successfully obtained the corresponding polypeptide through polycondensation accompanying the elimination of phenol and CO₂ in high yield. The molecular weight of polypeptide was adjusted by varying the feed ratio of urethane derivative to amine. MALDI-TOF mass analysis revealed that the added amine was successfully incorporated into the terminal end of the polypeptide. Taking advantage of our facile synthetic route to synthesize a polypeptide, we have synthesized a polystyrenes bearing oligo(L-methionine sulfoxide) in the side chain, and investigated their application as a surface-coating polymer that leads to antifouling property against proteins and cells. The polystyrene was readily synthesized through polycondensation of a urethane derivative of L-methionine sulfoxide in the presence of 4-vinylbenzylamine, followed by radical polymerization with water-soluble azo initiator. The inhibition of protein (hRP-IgG) adsorption and F9 cells adhesion was observed on the surface of the polymer-coated PS plate because of the hydrophilic nature of L-methionine sulfoxide segment. In addition, the result of CCK-8 assay reveals a low cytotoxicity against F9 cells, indicating that the polymer possesses a high biocompatibility.