title: Synthesis of hyperbranched polypeptide and PEO block copolymer by consecutive thiol-yne chemistry.
abstract: Hyperbranched poly(ε-benzyloxycarbonyl-L-lysine) (HPlys) with multiple alkyne peripheries was synthesized through the click polycondensation of an AB2 type Plys macromonomer with α-thiol and ω-alkyne terminal groups (thiol is the A unit, and each π bond in alkyne is the B unit), and the resulting HPlys was further conjugated with thiol-termined poly(ethylene oxide) (PEO) to generate HPlys-b-PEO block copolymer by consecutive thiol-yne chemistry. Their molecular structures and physical properties were characterized in detail by FT-IR, (1)H NMR, gel permeation chromatography, differential scanning calorimetry, wide-angle X-ray diffraction, and polarized optical microscopy. HPlys and HPlys-b-PEO mainly assumed an α-helix conformation similar to the linear precursors, while the liquid crystalline phase transition of Plys segment disappeared within HPlys and HPlys-b-PEO. HPlys-b-PEO self-assembled into nearly spherical micelles in aqueous solution, while it gave a 5-fold lower critical aggregation concentration (8.9 × 10(-3) mg/mL) than a linear counterpart (4.5 × 10(-2) mg/mL), demonstrating a dendritic topology effect. Compared with a linear counterpart, HPlys-b-PEO gave a higher drug-loading capacity and efficiency for the anticancer drug doxorubicin (DOX) and a slower drug-release rate with an improved burst-release profile, enabling them useful for drug delivery systems. Importantly, this work provides a versatile strategy for the synthesis of hyperbranched polypeptides and related block copolymers by utilizing thiol-yne chemistry.
authors: Department of Polymer Science & Engineering, School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai 200240, PR China.
authors: Xiao
authors: X
authors: Chang
authors: Chang-Ming
authors: CM
authors: Dong
mesh_terms: D000480:Alkynes / Q000138:chemical synthesis; D000903:Antibiotics, Antineoplastic / Q000737:chemistry; D002152:Calorimetry, Differential Scanning; D057930:Click Chemistry; D050091:Dendrimers / Q000138:chemical synthesis*; D004317:Doxorubicin / Q000737:chemistry; D007700:Kinetics; D008823:Micelles; D053758:Nanoparticles / Q000737:chemistry; D010316:Particle Size; D011095:Polyethylenes / Q000138:chemical synthesis*; D011107:Polylysine / Q000031:analogs & derivatives* / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis; D014961:X-Ray Diffraction
chemical_list: D000480:Alkynes; D000903:Antibiotics, Antineoplastic; D050091:Dendrimers; D008823:Micelles; D011095:Polyethylenes; D013438:Sulfhydryl Compounds; D011107:Polylysine; C038295:poly(N(epsilon)-benzyloxycarbonyl-L-lysine); D004317:Doxorubicin