Effect Of Chirality On Conformation And Properties Of Polypeptides

Polypeptides and their amphiphilic block copolymers have important application prospects in drug controlled release system,nanomedicine and other fields.As we know,in the organisms and biological processes,chirality greatly affects the biological activities and functions for optically active small molecules and macromolecules.It is important to control drug release and delivery by changing the chirality of the polymer.However,there are few reports about the influence of chirality on the conformation and properties of polypeptides.Poly?S-o-nitrobenzyl L,D-cysteine??L,D-PNBC?,polyethylene glycol-block-poly?S-o-nitrobenzyl L,D-cysteine??PEO-b-L,D-PNBC?and polyethylene glycol-block-poly??-benzyl L,D-glutamate ester??PEO-b-L,D-PBLDG?block copolymer were synthesized by ring-opening polymerization?ROP?.And the effect of chirality on their conformation and properties was studied in detail.?1?Effect of chirality on conformation and properties of poly?S-?o-nitrobenzyl?L,D-cysteine?polypeptidesTwo kinds of photoresponsive S-?o-nitrobenzyl?-L,D-cysteine N-carboxyanhydride?L,D-NBC-NCA?monomer and related a series of poly?S-?o-nitrobenzyl?L,D-cysteine?polypeptides?L,D-PNBC?with different chirality were synthesized and their molecular structures,secondary conformations,physical and chemical properties were thoroughly investigated by Infrared spectroscopy?FT-IR?,Nuclear Magnetic Resonance Spectroscopy?¹H NMR?,Gel permeation chromatography?GPC?,Differential Scanning Calorimetry?DSC?,Wide-angle X-ray diffraction?WXRD?and Circular dichroism?CD?spectra.The nanoparticles with different chiral polymers were prepared by nanoprecipitation and drug loading,release properties and cytotoxicity of the nanoparticles were studied.The cellular uptake behavior of drug loading nanoparticles with different chirality was investigated by flow cytometry and fluorescence microscopy.The results indicated that the optical properties of polymer was controlled by the composition of the chiral units and the secondary conforamtion of PNBC was regulated by chirality and the degree of polymerization.What's more,the L-configuration polymer loaded nanoparticles were more easily to enter into the cell.?2?Effect of chirality on conformation and properties of polyethylene glycol-block-poly?S-o-nitrobenzyl L,D-cysteine?copolymerFirst the macromolecular initiator amine-terminated polyethylene glycol?PEO-NH₂?was synthesized,and then used to initiate S-?o-nitrobenzyl?-L,D-cysteine N-carboxyanhydride?L,D-NBC-NCA?monomer by ring-opening polymerization?ROP?in DMF solution at 25°C to synthesize polyethylene glycol-block-poly?S-o-nitrobenzyl L,D-cysteine??PEO-b-PBLDG?copolymer with different chirality.The o-nitrobenzyl?NB?groups were removed after photocleavage.Their molecular structures and secondary conformation of PEO-b-L,D-PNBC copolymers were thoroughly investigated by FT-IR,¹H NMR,GPC and CD.The nanoparticles with different chiral block copolymers were prepared by self-assembly method and drug loading,release properties,cytotoxicity and cellular uptake behavior of the nanoparticles were thoroughly studied.It was found that the optical property of block copolymers was still decided by the composition of chiral units and the introduction of PEO segments had no effect on their optical rotation.Secondary conformation of the copolymer was affected by PEO segments and chirality of PNBC segments,and the removal of NB groups facilitates the randomization of the block copolymers.Meanwhile NB group and chirality of PNBC segments collaboratively regulated the cellular uptake behavior of copolymers loading nanoparticles and NB group shedding makes the intracellular ability of nanoparticles decreased,while the L-configuration copolymer was more conducive to enter into cells.?3?Effect of chirality on conformation and properties of polyethylene glycol-block-poly??-benzyl L,D-glutamate ester?copolymerTwo kinds of chiral glutamic acid benzyl ester-N-carboxy anhydride?BLG-NCA,BDG-NCA?monomer were synthesized and the related polyethylene glycol-block-poly??-benzyl L,D-glutamate ester??PEO-b-PBLDG?copolymers were synthesized with macromolecular initiator PEO-NH₂ by ROP in DMF solution at 25°C.Their molecular structures and secondary conformation of PEO-b-PBLDG copolymers were thoroughly investigated by FT-IR,¹H NMR and GPC.The nanoparticles with different?-helix chiral block copolymers were prepared by self-assembly method and drug loading,release properties,cytotoxicity and cellular uptake behavior of the nanoparticles were comparatively investigated.It was indicated that?-helix conformation of the copolymer was influenced by PEO segments and chirality of PBLDG segments and the drug loading nonaparticles of L-configuration copolymer was better in cell endocytosis.