Amino acid N-carboxyanhydrides and polypeptides: Controlled polymerization, properties and applications

N-carboxyanhydrides (nca);Polypeptides;Controlled-polymerization;Helix gene-delivery

Lu, Hua

关键词: N-carboxyanhydrides (nca);    Polypeptides;    Controlled-polymerization;    Helix gene-delivery;   

Others  :  https://www.ideals.illinois.edu/bitstream/handle/2142/24190/Lu_Hua.pdf?sequence=1&isAllowed=y

美国|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

The goal of my Ph.D. research is to develop controlled/living polymerization techniques of α-amino acid N-carboxyanhydrides (NCAs) and synthetic polypeptides based materials. Polypeptides are a class of emerging biomaterials receiving increasing interests for various applications including drug delivery, gene therapy, antimicrobial and tissue engineering. The ring-opening polymerization (ROP) of NCAs has long been demonstrated as a powerful technique for preparation of high molecular weight (MW) synthetic polypeptides in gram scale.We developed a system utilizing organo-silicon amines, namely hexamethyldisilazane (HMDS) and N-trimethylsilyl (N-TMS) amines, for the controlled ROP of various NCAs.Predicable MWs and narrow molecular weight distributions (MWDs) of homo- and block- polypeptides can be prepared via this methodology. Our mechanism study illustrated that the polymerization involves formation of trimethylsilyl carbamate (TMS-CBM) structure at the propagation center. In addition, the system allows facile end group and side-chain functionalization of the polypeptides and integration of NCA ROP with other polymerization techniques such as ring-opening metathesis polymerization (ROMP) to prepare hybrid polypeptides materials. Finally, we discovered a new type of ionic polypeptides with unusual helical stability and demonstrated that they have great potential for gene delivery and siRNA delivery applications.