Facile preparation of well-defined AB>₂ Y-shaped miktoarm star polypeptide copolymer via the combination of ring-opening polymerization and click chemistry

Well-defined AB₂ Y-shaped miktoarm star polypeptide copolymer, PZLL-β-(PBLG)₂, was synthesized via a combination of ring-opening polymerization (ROP) of α-amino acid N-carboxyanhydride (NCA) and click chemistry, where PZLL is poly(ε-benzyloxycarbonyl-L-lysine) and PBLG is poly(y-benzyl-L-glutamate). First, two types of primary-amine-containing initiators, N-aminoethyl 3,5-bis(propargyloxyl)-benzamide and 3-azidopropylamine, were synthesized and employed for the ROP of NCA, leading to the formation of dialkynyl-terminated PZLL and azide-terminated PBLG, dialkynyl-PZLL and PBLG-N₃, respectively. The subsequent copper(I)-catalyzed cycloaddition reaction between dialkynyl-PZLL and slightly excess PBLG-N₃ led to facile preparation of PZLL-b-(PBLG)₂ Y-shaped miktoarm star polypeptide copolymer. The excess PBLG-N₃ was scavenged off by reacting with alkynyl-functionalized Wang resin. The obtained Y-shaped miktoarm star polypeptide copolymer was characterized by gel permeation chromatograph (GPC), Fourier transform-infrared spectroscopy (FF-IR), and ¹H NMR. Moreover, after the hydrolysis of protecting benzyl and benzyloxycarbonyl groups of PZLL-b-(PBLG)₂, water-soluble pH-responsive Y-shaped miktoarm star polypeptide copolymer, PLL-b-(PLGA)₂, was obtained, where PLL is poly(L-lysine) and PLGA is poly(L-glutamic acid). It can self-assemble into PLGA-core micelles at acidic pH and PLL-core micelles at alkaline pH, accompanied with the coil-to-helix transition of PLGA and PLL sequences, respectively. The spontaneous pH-responsive supramolecular assembly of PLL-b-(PLGA)₂ miktoarm star polypeptide copolymer has been investigated via a combination of ¹H NMR, laser light scattering (LLS), transmission electron microscopy (TEM), and circular dichroism (CD) spectroscopy.