A Simple and Versatile Synthetic Strategy to Functional Polypeptides via Vinyl Sulfone-Substituted l-Cysteine N-Carboxyanhydride
Jianren Zhou , Peipei Chen , Chao Deng *（邓超）, Fenghua Meng , Ru Cheng , and Zhiyuan Zhong * （钟志远）
Biomedical Polymers Laboratory, and Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, People’s Republic of China
Macromolecules 2013, 46, 6723–6730
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.
链接： //pubs.acs.org/doi/abs/10.1021/ma4014669
