Polypeptide brushes are attractive platforms to generate functional and responsive interfaces that are of potential interest due to their possible biodegradability, biocompatibility and tunable secondary structures. S...Polypeptide brushes are attractive platforms to generate functional and responsive interfaces that are of potential interest due to their possible biodegradability, biocompatibility and tunable secondary structures. Surface-initiated ringopening polymerization（SI-ROP） of α-amino acid N-carboxyanhydrides represents a powerful and versatile strategy to generate polypeptide brushes. This review is an attempt to capture the state-of-the-art in this field and highlights the latest developments in several selected areas. In addition to presenting an overview of the synthetic methods that have been used to generate polypeptide brushes via SI-ROP, this article will discuss the preparation of patterned polypeptide brushes, the conformational properties of surface-tethered polypeptides, ways to control chain orientation at surfaces as well as properties and applications of these thin polymer films.展开更多
The recent advances in accelerated polymerization of N-carboxyanhydrides (NCAs) offer an effective strategy to simplify the preparation of polypeptide materials. However, the fine-tuning of polymerization kinetics, wh...The recent advances in accelerated polymerization of N-carboxyanhydrides (NCAs) offer an effective strategy to simplify the preparation of polypeptide materials. However, the fine-tuning of polymerization kinetics, which is critical to differentiate the main polymerization and the side reactions, remains largely unexplored. Herein we report the modulation of polymerization rate of NCA in a water/oil biphasic system. By altering the aqueous pH, the initial location of the initiators, and the pK_(a) of initiating amines, we observed the change in polymerization time from several minutes to a few hours. Due to the high interfacial activity and low pKa value, controlled polymerization was observed from multi-amine initiators even if they were initially located in the aqueous phase. This work not only improves our understanding on the biphasic polymerization mechanism, but also facilitates preparation of versatile polypeptide materials.展开更多
Polypeptoids have been explored as mimics of polypeptides,owing to polypeptoids'superior stability upon proteolysis.Polypeptoids can be synthesized from one-pot ring-opening polymerization of amino acid N-substitu...Polypeptoids have been explored as mimics of polypeptides,owing to polypeptoids'superior stability upon proteolysis.Polypeptoids can be synthesized from one-pot ring-opening polymerization of amino acid N-substituted N-carboxyanhydrides(NNCAs).However,the speed of polymerization of NNCAs can be very slow,especially for NNCAs bearing a bulky N-substitution group.This hindered the exploration on polypeptoids with more diverse structures and functions.Therefore,it is in great need to develop advanced strategies that can accelerate the polymerization on inactive NNCAs.Hereby,we report that lithium/sodium/potassium hexamethyldisilazide(Li/Na/KHMDS)initiates a substantially faster polymerization on NNCAs than do commonly used amine initiators,especially for NNCAs with bulky N-substitution group.This fast NNCA polymerization will increase the structure diversity and application of polypeptoids as synthetic mimics of polypeptides.展开更多
Poly(amino acid)has been widely utilized in drug delivery,tissue engineering and biomedical materials.The biomaterials based on poly(glutamic acid)are usually modified via copolymerization with other monomers such as ...Poly(amino acid)has been widely utilized in drug delivery,tissue engineering and biomedical materials.The biomaterials based on poly(glutamic acid)are usually modified via copolymerization with other monomers such as L-aspartic acid to improve the uncontrolled degradation rate.The ring-opening homo- and co-polymerization ofγ-benzyl-L-glutamate N-carboxyanhydride(BLG-NCA)andβ-benzyl-L-aspartate N-carboxyanhydride(BLA-NCA)were carried out in solution by using triethylamine(TEA)as initiator.The BLG-NCA homopol...展开更多
The amphiphilic multiarm copolymers were synthesized through the modification of commercially available hyperbranched polyesters（Boltorn H40） with N-ε-carbobenzoxy-L-Lysine N-carboxyanhydride（ZLys-NCA）.After bein...The amphiphilic multiarm copolymers were synthesized through the modification of commercially available hyperbranched polyesters（Boltorn H40） with N-ε-carbobenzoxy-L-Lysine N-carboxyanhydride（ZLys-NCA）.After being condensed with N-Boc-phenylalanine（Boc-^NPhe） and deprotected the Boc-groups in trifluoroacetic acid（TFA）,the original terminal hydroxyl groups were transformed into the amino groups and then initiated the ring-opening polymerization of ZLys-NCA.The hydrophilic poly（L-lysine） was grafted to the surface of Boltorn H40 successfully after the protecting benzyl groups were removed by the HBr solution in glacial acetic acid（33 wt%）.The resulting multiarm copolymers were characterized by the ^1H-NMR,GPC and FTIR.The arm length calculated by NMR and GPC analysis was about 3 and 13 lysine-units for H40-Phe-PLysl and H40-Phe-PLys2 respectively.Due to the amphiphilic molecular structure,they displayed ability to self-assemble into spherical micelles in aqueous solution with the average diameter in the range from 70 nm to 250 nm.The CMC of H40-Phe-PLysl and H40-Phe-PLys2 was 0.013 mg/mL and 0.028 mg/mL,respectively, indicating that H40-Phe-PLysl with shorter arm length is easier to self-assemble than H40-Phe-PLys2 with longer arm length.展开更多
A series of poly（L-glutamate）s grafted with oligo（ethylene glycol） （OEG） side-chains through the thioether linkages （PALGn-g-EGx, x = 2, 3 and 4） were prepared by ring-opening polymerization （ROP） of γ-ally...A series of poly（L-glutamate）s grafted with oligo（ethylene glycol） （OEG） side-chains through the thioether linkages （PALGn-g-EGx, x = 2, 3 and 4） were prepared by ring-opening polymerization （ROP） of γ-allyl-L-glutamate N-carboxyanhydride （ALG-NCA） and thiol-ene photoaddition. The chemical structures and physical properties were characterized by 1H-NMR, Fourier transform infrared （FTIR）, circular dichroism （CD）, etc. The PALGn-g-EGx samples with x = 3 and 4 displayed lower critical solution temperature （LCST） in water due to the presence of OEG units. The clouding point （CP） of polypeptides can be finely tuned by changing the side chain structures, molecular weights and sample concentrations. In addition, the thioether linkages in the side chains offer additional redox-responsive properties. The influence of both OEG units and thioether linkages on the LCST behavior was systematically investigated. This work provides an efficient way to prepare multi-stimuli responsive materials with highly tunable properties.展开更多
In polymerization of N-carboxyanhydride-L-α-arginine(L-Arg-NCA) in H2O,nucleophilic reaction of guanidine group with the carbonyl group of L-Arg-NCA leads to quick intramolecular rearrangement,yielding a 6-membered r...In polymerization of N-carboxyanhydride-L-α-arginine(L-Arg-NCA) in H2O,nucleophilic reaction of guanidine group with the carbonyl group of L-Arg-NCA leads to quick intramolecular rearrangement,yielding a 6-membered ring intermediate 1-amidino-3-amino-2-piperidone,which is either elongated by another L-Arg-NCA yielding arginyl-1-amidino-3-amino-2-piperidone or hydrolyzed to L-α-arginine.The oligoarginines are formed mainly through hydrolysis of arginyl-1-amidino-3-amino-2-piperidones.This is a unique pathway in polymerization of L-Arg-NCA with regard to the usual pathway of elongations by reaction of N-carboxyanhydride-L-α-amino acid with L-α-amino acid or oligopeptides.展开更多
A series of ABA triblock copolymers of poly(?-(2-methoxy ethoxy)esteryl-glutamate)-block-poly(ethylene glycol)-blockpoly(?-(2-methoxy ethoxy)esteryl-glutamate) with poly(ethylene glycol) as middle hydrophilic B block ...A series of ABA triblock copolymers of poly(?-(2-methoxy ethoxy)esteryl-glutamate)-block-poly(ethylene glycol)-blockpoly(?-(2-methoxy ethoxy)esteryl-glutamate) with poly(ethylene glycol) as middle hydrophilic B block and oligo(ethylene glycol)-functionalized polyglutamate(poly-L-EG2Glu) as terminal A blocks were prepared via ring-opening polymerization of EG2 Glu N-carboxyanhydride(NCA). The resulting P(EG2Glu)-b-PEG-b-P(EG2Glu) triblocks can spontaneously form hydrogels in water. The intermolecular hydrogen bonding interactions between polypeptides blocks were responsible for the formation of gel network structure. These hydrogels displayed shear-thinning and rapid recovery properties, which endowed them potential application as injectable drug delivery system. The mechanical strength of hydrogels can be modulated by copolymer composition, molecular weight and concentrations. Also, it was found that the hydrogels' strength decreased with temperature due to dehydration of polypeptide segments. Atomic force microscopy and scanning electron microscopy images revealed that these hydrogels were formed through micelle packing mechanism. Circular dichroism and Fourier transform infrared spectroscopy characterizations suggested the poly-L-EG2 Glu block adopted mixed conformation. A preliminary assessment of drug release in vitro demonstrated the hydrogels can offer a sustained release of doxorubicin(DOX) and the release rate could be controlled by varying chemical composition.展开更多
Novel, self-associating hybrid copolymers were synthesized via controlled ring-opening polymerization of N-carboxyanhydride of Z-L-lysine (Z-L-Lys-NCA), initiated by amino-functional macroinitiators. A poly(N-isopropy...Novel, self-associating hybrid copolymers were synthesized via controlled ring-opening polymerization of N-carboxyanhydride of Z-L-lysine (Z-L-Lys-NCA), initiated by amino-functional macroinitiators. A poly(N-isopropylacry-lamide) (PNIPAm)-based macroinitiator containing 10 mol% of polyoxyethylene grafts and a terminal primary amine group in the form of ammonium hydrochloride (PNIPAm-g-PEО) was synthesized and used to initiate the ammonium- mediated ring-opening polymerization of NCA described by Dimitrov and Schlaad [1]. Thus, hybrid copolymers ((PNIPAm-g-PEO)-b-PLys) with controlled molar-mass characteristics and functionality were obtained. The potential applications of PNIPAm-based copolymers in the systems for controlled drug release, immobilization of enzymes and protein purification have aroused great interest in the studies of their properties and behaviour. The thermal stability and thermodynamic properties of the copolymers obtained were studied. The differential thermal analysis of polyfunctional hybrid copolymers (PNIPAm-g-PEO)-b-PLys) showed that thermooxidative destruction occurs in two stages: primary, of the unstable fragments (grafted chains of PEO);and secondary, of the main polymer chains of poly(N-isopropylacry-lamide) and poly(L-lysine). The kinetics of thermal degradation was evaluated and the values of the activation energy of the degradation process, changes of Gibbs free energy, enthalpy and entropy for the formation of the activated complex were also calculated.展开更多
Triphosgene was used to react with γ-chloroethyl glutamate, which was synthesized from 2-ethylene chlorohydrin and L-glutamic acid, to give γ-chloroethyl glutamate N-carboxyan.hydride (NCA). Thus, poly(γ-chloroethy...Triphosgene was used to react with γ-chloroethyl glutamate, which was synthesized from 2-ethylene chlorohydrin and L-glutamic acid, to give γ-chloroethyl glutamate N-carboxyan.hydride (NCA). Thus, poly(γ-chloroethyl glutamate), a new poly (amino acid) with reactive chloride, was obtained from the NCA by using triethylamine as the initiator which can lead to intrinsic viscosity of polypeptide, [η], over 50 mL/g. NCA and polymer were characterized by IR, 1H NMR and 13C NMR. Oligomer of γ-chloroethyl glutamate was also obtained while NCA was initiated by moisture in air. The conforma- tions of oligomer and polymer of γ-chloroethyl glutamate were observed by IR and CD spectroscopy. The results suggested that the conformation of oligomer mainly be β-sheet, while the polymer be α-helix.展开更多
基金financially supported by the Sino-Swiss Science and Technology Cooperation(No.EG41-092011)as well as the Chinese Academy of Sciences(Visiting Professorship for Senior International Scientists to H.A.K.)
文摘Polypeptide brushes are attractive platforms to generate functional and responsive interfaces that are of potential interest due to their possible biodegradability, biocompatibility and tunable secondary structures. Surface-initiated ringopening polymerization（SI-ROP） of α-amino acid N-carboxyanhydrides represents a powerful and versatile strategy to generate polypeptide brushes. This review is an attempt to capture the state-of-the-art in this field and highlights the latest developments in several selected areas. In addition to presenting an overview of the synthetic methods that have been used to generate polypeptide brushes via SI-ROP, this article will discuss the preparation of patterned polypeptide brushes, the conformational properties of surface-tethered polypeptides, ways to control chain orientation at surfaces as well as properties and applications of these thin polymer films.
基金the National Natural Science Foundation of China(No.22101194 for Z.Song and No.52233015 for J.Cheng)Natural Science Foundation of Jiangsu Province(No.BK20210733 for Z.Song)+1 种基金Suzhou Municipal Science and Technology Bureau(No.ZXL2021447 for Z.Song)Collaborative Innovation Center of Suzhou Nano Science&Technology,the 111 Project.,Joint International Research Laboratory of Carbon-Based Functional Materials and Devices,and Suzhou Key Laboratory of Nanotechnology and Biomedicine.
文摘The recent advances in accelerated polymerization of N-carboxyanhydrides (NCAs) offer an effective strategy to simplify the preparation of polypeptide materials. However, the fine-tuning of polymerization kinetics, which is critical to differentiate the main polymerization and the side reactions, remains largely unexplored. Herein we report the modulation of polymerization rate of NCA in a water/oil biphasic system. By altering the aqueous pH, the initial location of the initiators, and the pK_(a) of initiating amines, we observed the change in polymerization time from several minutes to a few hours. Due to the high interfacial activity and low pKa value, controlled polymerization was observed from multi-amine initiators even if they were initially located in the aqueous phase. This work not only improves our understanding on the biphasic polymerization mechanism, but also facilitates preparation of versatile polypeptide materials.
基金This research was supported by the National Natural Science Foundation of China(Nos.22075078,21774031,21861162010)the Natural Science Foundation of Shanghai(No.118ZR1410300)+3 种基金the National Key Research and Development Program of China(No.2016YFC1100401)the National Natural Science Foundation of China for Innovative Research Groups(No.51621002)Program of Shanghai Academic/Technology Research Leader(No.20XD1421400)Research program of State Key Laboratory of Bioreactor Engineering,the Fundamental Research Funds for the Central Universities(No.22221818014).
文摘Polypeptoids have been explored as mimics of polypeptides,owing to polypeptoids'superior stability upon proteolysis.Polypeptoids can be synthesized from one-pot ring-opening polymerization of amino acid N-substituted N-carboxyanhydrides(NNCAs).However,the speed of polymerization of NNCAs can be very slow,especially for NNCAs bearing a bulky N-substitution group.This hindered the exploration on polypeptoids with more diverse structures and functions.Therefore,it is in great need to develop advanced strategies that can accelerate the polymerization on inactive NNCAs.Hereby,we report that lithium/sodium/potassium hexamethyldisilazide(Li/Na/KHMDS)initiates a substantially faster polymerization on NNCAs than do commonly used amine initiators,especially for NNCAs with bulky N-substitution group.This fast NNCA polymerization will increase the structure diversity and application of polypeptoids as synthetic mimics of polypeptides.
文摘Poly(amino acid)has been widely utilized in drug delivery,tissue engineering and biomedical materials.The biomaterials based on poly(glutamic acid)are usually modified via copolymerization with other monomers such as L-aspartic acid to improve the uncontrolled degradation rate.The ring-opening homo- and co-polymerization ofγ-benzyl-L-glutamate N-carboxyanhydride(BLG-NCA)andβ-benzyl-L-aspartate N-carboxyanhydride(BLA-NCA)were carried out in solution by using triethylamine(TEA)as initiator.The BLG-NCA homopol...
基金supported by the National Basic Research Program(Nos.2007CB808000,2009CB930400)the National Natural Science Foundation of China(Nos.50873058,20874060,50633010)+1 种基金Shanghai Leading Academic Discipline Project(No.B202)the Zhejiang Provincial Natural Science Foundation of China(No.Y405411)
文摘The amphiphilic multiarm copolymers were synthesized through the modification of commercially available hyperbranched polyesters（Boltorn H40） with N-ε-carbobenzoxy-L-Lysine N-carboxyanhydride（ZLys-NCA）.After being condensed with N-Boc-phenylalanine（Boc-^NPhe） and deprotected the Boc-groups in trifluoroacetic acid（TFA）,the original terminal hydroxyl groups were transformed into the amino groups and then initiated the ring-opening polymerization of ZLys-NCA.The hydrophilic poly（L-lysine） was grafted to the surface of Boltorn H40 successfully after the protecting benzyl groups were removed by the HBr solution in glacial acetic acid（33 wt%）.The resulting multiarm copolymers were characterized by the ^1H-NMR,GPC and FTIR.The arm length calculated by NMR and GPC analysis was about 3 and 13 lysine-units for H40-Phe-PLysl and H40-Phe-PLys2 respectively.Due to the amphiphilic molecular structure,they displayed ability to self-assemble into spherical micelles in aqueous solution with the average diameter in the range from 70 nm to 250 nm.The CMC of H40-Phe-PLysl and H40-Phe-PLys2 was 0.013 mg/mL and 0.028 mg/mL,respectively, indicating that H40-Phe-PLysl with shorter arm length is easier to self-assemble than H40-Phe-PLys2 with longer arm length.
基金financially supported by the National Natural Science Foundation of China(Nos.20974112 and 50821062)
文摘A series of poly（L-glutamate）s grafted with oligo（ethylene glycol） （OEG） side-chains through the thioether linkages （PALGn-g-EGx, x = 2, 3 and 4） were prepared by ring-opening polymerization （ROP） of γ-allyl-L-glutamate N-carboxyanhydride （ALG-NCA） and thiol-ene photoaddition. The chemical structures and physical properties were characterized by 1H-NMR, Fourier transform infrared （FTIR）, circular dichroism （CD）, etc. The PALGn-g-EGx samples with x = 3 and 4 displayed lower critical solution temperature （LCST） in water due to the presence of OEG units. The clouding point （CP） of polypeptides can be finely tuned by changing the side chain structures, molecular weights and sample concentrations. In addition, the thioether linkages in the side chains offer additional redox-responsive properties. The influence of both OEG units and thioether linkages on the LCST behavior was systematically investigated. This work provides an efficient way to prepare multi-stimuli responsive materials with highly tunable properties.
基金Supported by the Special Research Project of Beijing Scientific and Technical Committee (Grant No. Z00063002040191)the Natural Basic Research Program of China (Grant No. 2007CB935901)
文摘In polymerization of N-carboxyanhydride-L-α-arginine(L-Arg-NCA) in H2O,nucleophilic reaction of guanidine group with the carbonyl group of L-Arg-NCA leads to quick intramolecular rearrangement,yielding a 6-membered ring intermediate 1-amidino-3-amino-2-piperidone,which is either elongated by another L-Arg-NCA yielding arginyl-1-amidino-3-amino-2-piperidone or hydrolyzed to L-α-arginine.The oligoarginines are formed mainly through hydrolysis of arginyl-1-amidino-3-amino-2-piperidones.This is a unique pathway in polymerization of L-Arg-NCA with regard to the usual pathway of elongations by reaction of N-carboxyanhydride-L-α-amino acid with L-α-amino acid or oligopeptides.
基金financially supported by the National Natural Science Foundation of China for Distinguished Young Scholar(51225306)the CAS-CSIRO Cooperative Research Program(GJHZ1408)
文摘A series of ABA triblock copolymers of poly(?-(2-methoxy ethoxy)esteryl-glutamate)-block-poly(ethylene glycol)-blockpoly(?-(2-methoxy ethoxy)esteryl-glutamate) with poly(ethylene glycol) as middle hydrophilic B block and oligo(ethylene glycol)-functionalized polyglutamate(poly-L-EG2Glu) as terminal A blocks were prepared via ring-opening polymerization of EG2 Glu N-carboxyanhydride(NCA). The resulting P(EG2Glu)-b-PEG-b-P(EG2Glu) triblocks can spontaneously form hydrogels in water. The intermolecular hydrogen bonding interactions between polypeptides blocks were responsible for the formation of gel network structure. These hydrogels displayed shear-thinning and rapid recovery properties, which endowed them potential application as injectable drug delivery system. The mechanical strength of hydrogels can be modulated by copolymer composition, molecular weight and concentrations. Also, it was found that the hydrogels' strength decreased with temperature due to dehydration of polypeptide segments. Atomic force microscopy and scanning electron microscopy images revealed that these hydrogels were formed through micelle packing mechanism. Circular dichroism and Fourier transform infrared spectroscopy characterizations suggested the poly-L-EG2 Glu block adopted mixed conformation. A preliminary assessment of drug release in vitro demonstrated the hydrogels can offer a sustained release of doxorubicin(DOX) and the release rate could be controlled by varying chemical composition.
文摘Novel, self-associating hybrid copolymers were synthesized via controlled ring-opening polymerization of N-carboxyanhydride of Z-L-lysine (Z-L-Lys-NCA), initiated by amino-functional macroinitiators. A poly(N-isopropylacry-lamide) (PNIPAm)-based macroinitiator containing 10 mol% of polyoxyethylene grafts and a terminal primary amine group in the form of ammonium hydrochloride (PNIPAm-g-PEО) was synthesized and used to initiate the ammonium- mediated ring-opening polymerization of NCA described by Dimitrov and Schlaad [1]. Thus, hybrid copolymers ((PNIPAm-g-PEO)-b-PLys) with controlled molar-mass characteristics and functionality were obtained. The potential applications of PNIPAm-based copolymers in the systems for controlled drug release, immobilization of enzymes and protein purification have aroused great interest in the studies of their properties and behaviour. The thermal stability and thermodynamic properties of the copolymers obtained were studied. The differential thermal analysis of polyfunctional hybrid copolymers (PNIPAm-g-PEO)-b-PLys) showed that thermooxidative destruction occurs in two stages: primary, of the unstable fragments (grafted chains of PEO);and secondary, of the main polymer chains of poly(N-isopropylacry-lamide) and poly(L-lysine). The kinetics of thermal degradation was evaluated and the values of the activation energy of the degradation process, changes of Gibbs free energy, enthalpy and entropy for the formation of the activated complex were also calculated.
文摘Triphosgene was used to react with γ-chloroethyl glutamate, which was synthesized from 2-ethylene chlorohydrin and L-glutamic acid, to give γ-chloroethyl glutamate N-carboxyan.hydride (NCA). Thus, poly(γ-chloroethyl glutamate), a new poly (amino acid) with reactive chloride, was obtained from the NCA by using triethylamine as the initiator which can lead to intrinsic viscosity of polypeptide, [η], over 50 mL/g. NCA and polymer were characterized by IR, 1H NMR and 13C NMR. Oligomer of γ-chloroethyl glutamate was also obtained while NCA was initiated by moisture in air. The conforma- tions of oligomer and polymer of γ-chloroethyl glutamate were observed by IR and CD spectroscopy. The results suggested that the conformation of oligomer mainly be β-sheet, while the polymer be α-helix.
基金supported by the National Natural Science Foundation of China(21374080,21674081,21611130175)Shanghai International Scientific Collaboration Fund,China(15230724500)+1 种基金Shanghai 1000 Talents PlanFundamental Research Funds for the Central Universities,China(0500219211,1500219107)
