N-Trimethylsilyl Amines for Controlled Ring-Opening Polymerization of Amino Acid N-Carboxyanhydrides and Facile End Group Functionalization of Polypeptides

摘要

Polypeptides have been extensively utilized in drug delivery, tissue engineering, sensing, and catalysis. To prepare polypeptides for these applications, it is essential to control their molecular weights (MWs) as well as their end groups during the ring-opening polymerizations (ROPs) of amino acid N-carboxyan-hydrides (NCAs). We recently reported hexamethyldisilazane (HMDS)-mediated, controlled NCA polymerization. This polymerization proceeds via a unique, trimethylsilyl carbamate (TMS-CBM) propagating group (Scheme la), which involves cleavage of the Si-N bond of HMDS during the initiation step. The resulting TMS-amine (red, Scheme la) opens the NCA ring at its CO-5 position to form a TMS-amide at the C-end while the TMS group (blue, Scheme la) is attached to the N-end to form a TMS-CBM (the propagating chain end). The propagation of polypeptide chains proceeds through the transfer of the TMS group from the terminal TMS-CBM to the incoming monomer and forms a new TMS-CBM propagating chain end (Scheme la). We postulate that when a 7V-TMS amine is used as the initiator, cleavage of its Si-N bond will generate an amine and a TMS group (Scheme 1b) that will subsequently form the corresponding amide at the C-end and a TMS-CBM at the N-end after NCA ring opening (Scheme lb). Thus, chain propagation should proceed in the same manner as HMDS-mediated polymerization (Scheme la). Because a large variety of N-TMS amines are readily available, this method should allow facile functionalization of the C-termini of polypeptides (Scheme lb).