A Simple and Versatile Synthetic Strategy to Functional Polypeptides via Vinyl Sulfone-Substituted l-Cysteine N-Carboxyanhydride

Vinyl sulfone-substituted l -cysteine N -carboxyanhydride (VSCys-NCA) monomer was designed and developed to afford a novel and versatile family of vinyl sulfone (VS)-functionalized polypeptides, which further offer a facile access to functional polypeptide-based materials including glycopolypeptides, functional polypeptide coatings, and in situ forming polypeptide hydrogels through Michael-type addition chemistry under mild conditions. VSCys-NCA was obtained in two straightforward steps with a high overall yield of 76%. The copolymerization of γ-benzyl l -glutamate NCA (BLG-NCA), N -benzyloxycarbonyl- l -lysine NCA (ZLL-NCA), or l -leucine NCA (Leu-NCA) with VSCys-NCA using 1,1,1-trimethyl- N -2-propenylsilanamine (TMPS) as an initiator proceeded smoothly in DMF at 40 °C, yielding P(BLG- co -VSCys), P(ZLL- co -VSCys), or P(Leu- co -VSCys) with defined functionalities, controlled molecular weights, and moderate polydispersities (PDI = 1.15–1.50). The acidic deprotection of P(BLG- co -VSCys) and P(ZLL- co -VSCys) furnished water-soluble VS-functionalized poly( l -glutamic acid) (P(Glu- co -VSCys)) and VS-functionalized poly( l -lysine) (P(LL- co -VSCys)), respectively. These VS-functionalized polypeptides were amenable to direct, efficient, and selective postpolymerization modification with varying thiol-containing molecules such as 2-mercaptoethanol, 2-mercaptoethylamine hydrochloride, l -cysteine, and thiolated galactose providing functional polypeptides containing pendant hydroxyl, amine, amino acid, and saccharide, respectively. The contact angle and fluorescence measurements indicated that polymer coatings based on P(Leu- co -VSCys) allowed direct functionalization with thiol-containing molecules under aqueous conditions. Moreover, hydrogels formed in situ upon mixing aqueous solutions of P(Glu- co -VSCys) and thiolated glycol chitosan at 37 °C. These vinyl sulfone-functionalized polypeptides have opened a new avenue to a broad range of advanced polypeptide-based materials.