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.

Branched and Dendritic Polymer Architectures: Functional Nanomaterials for Therapeutic Delivery

“…The AB2 thiol-yne step growth approach to long chain hyperbranched polymers has also been employed by Dong et al, who synthesised hyperbranched polypeptide with a PEG shell for encapsulation and delivery of doxorubicin. 128 The researchers produced poly(e-benzyloxycarbonyl-L-lysine) with thiol and alkyne end groups which formed hyperbranched polylysine under UV irradiation, to which a linear PEG shell was attached. The hyperbranched polymer gave a higher drug loading than the linear counterpart block copolymer, and a slower drug release rate.…”

Amphiphilic copolymers with pendent carboxyl groups for high-efficiency loading and controlled release of doxorubicin

“…mPEG-b-PATMC-g-SCH 2 COOH was synthesized by the thiol-ene "click" reaction [25][26][27]. 0.28 g (0.801 mmol allyl groups) of mPEGb-PATMC was dissolved in 3 ml of anhydrous tetrahydrofuran (THF) followed by adding 4.003 mmol (0.368 g) of thioglycolic acid and 4.003 mmol (0.657 g) of AIBN under a N 2 atmosphere.…”

Comb-like poly(l-cysteine) derivatives with different side groups: synthesis via photochemistry and click chemistry, multi-responsive nanostructures, triggered drug release and cytotoxicity

“…[17][18][19][20][21][22][23][24][25][26][27][28][29][30] Increasing efforts have been made to produce side-chain modified polypeptides and functionalized polypeptides with tunable conformations by using the post-polymerization and/or ring opening polymerization (ROP) of functional α-amino acid N-carboxyanhydride (NCA) methods. [32][33][34][35][36][37][38][39][40][41] However, the click synthesis of comb-like graft polypeptides having different side groups is still limited and the relationship between the grafting ratios and the secondary structures are not fully understood. [32][33][34][35][36][37][38][39][40][41] However, the click synthesis of comb-like graft polypeptides having different side groups is still limited and the relationship between the grafting ratios and the secondary structures are not fully understood.…”