Efficient Preparation Of Cationic Helical Polypeptide And The Study Of Antimicrobial Activity

The continuous emergence of drug-resistant bacteria poses a serious threat to human health.Antimicrobial peptides are considered a powerful weapon against drug-resistant bacteria.However,the high production cost and high toxicity of this type of material restrict its development.The cationic polypeptide can imitate the structure and function of the antibacterial peptide,and an antibacterial polypeptide material with high antibacterial activity and low toxicity can be obtained through the adjustment of structural parameters.Efficient and controllable ring-opening polymerization preparation method provides a guarantee for reducing the preparation cost of polypeptide materials.This thesis explored the polymerization conditions of diamino initiators to polymerize N-carboxyanhydride(NCA)monomers in low polarity solvents,combined with efficient side chain modification methods,and obtained cationic helical polypeptide antibacterial material with high antibacterial properties and low toxicity.The specific research content is as follows:In the second chapter,a series of cationic helical polypeptides imidazolium conjugates were prepared by ring-opening polymerization(ROP)N-carboxyanhydride(CPBLG-NCA)initiated by various mono-or diamine initiators and subsequent side-chain modification with high grafting efficiency.Rapid and controlled ROP was achieved by polymerize the CPBLG-NCA in dichloromethane/Na HCO₃/H₂O solvent mixture with the amine initiators.The resulting cationic helical polypeptides bearing imidazolium iodide pendants showed reversible upper critical solution temperature(UCST)-type thermoresponsive properties in both ethanol and DI water while the polypeptides with tetrafluoroborate counter-anions showed a UCST in phosphate buffer saline(PBS).The cloud point temperature(T_cp)in ethanol,DI-H₂O and PBS solutions can be tuned by both molecular weight and the end-or linkage-groups in the main-chain.The cationic helical polypeptides showed good antibacterial activity against S.aureus and low hemolysis.In the third chapter,a series of triblock copolypeptides with chloro groups(PPG_n-PCPBLG_ms)and different main-chain lengths were synthesized via an ultra-fast ring opening polymerization(ROP)of purified or nonpurified CPBLG-NCA)using poly(propylene glycol)bis(2-aminopropyl ether)as the initiators.PPG_n-PCPBLG_mwith 90 degree of polymerization can be readily prepared within 300 s.Imidazolium-based block cationic helical copolypeptides(PPG_n-PIL_ms)were facile prepared via nucleophilic substitution of PPG_n-PCPBLG_m with Na N₃ and subsequent 1,3-dipolar cycloaddition.PPG_n-PIL_ms adopted?-helical conformation in both solid-states and aqueous solutions.They self-assembled into nanostructured and cationic micelles which displayed high potent antimicrobial activity against both Gram-positive and Gram-negative bacteria(i.e.,S.aureus and E.coli)and low hemolysis.The top-performing material,namely PPG₃₄-PIL₇₀ exhibited low minimum inhibitory concentration(MIC=25?g·m L^-1)against both S.aureus and E.coli.It also displayed low toxicity against various mammalian cell lines(i.e.,NIH 3T3,and 293T)at 2×MIC.