A Simple and Versatile Synthetic Strategy to Functional Polypeptides via Vinyl Sulfone-Substituted L?Cysteine N?Carboxyanhydride
作者：Jianren Zhou, Peipei Chen, Chao Deng*, Fenghua Meng, Ru Cheng, and Zhiyuan Zhong*
關鍵字：Ring-Opening Polymerization, N-Carboxyanhydride, Polypeptides, Vinyl Sulfone, Michael Addition, Hydrogels
論文來源：期刊
具體來源：Macromolecules
發表時間：2013年
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, as well as 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 leucine NCA (Leu-NCA) with VSCys-NCA using 1,1,1-trimethyl-N-2-propenyl-silanamine (TMPS) as an initiator proceeded smoothly in DMF at 40 oC, 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-VSCys)) and VS-functionalized poly(L-lysine) (P(LL-VSCys)), respectively. These VS-functionalized polypeptides were amenable to direct, efficient and selective post-polymerization 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.