3190-71-4Relevant articles and documents
Two-Dimensional Supramolecular Assemblies from pH-Responsive Poly(ethyl glycol)-b-poly(l -glutamic acid)-b-poly(N-octylglycine) Triblock Copolymer
Ni, Yunxia,Sun, Jing,Wei, Yuhan,Fu, Xiaohui,Zhu, Chenhui,Li, Zhibo
, p. 3367 - 3374 (2017)
Amphiphilic block copolymers containing polypeptides can self-assemble into a variety of nonspherical structures arising from strong interactions between peptide units. Here, we report the synthesis of a pH-responsive poly(ethyl glycol)-block-poly(l-glutamic acid)-block-poly(N-octylglycine) (PEG-b-PGA-b-PNOG) triblock copolymers by sequential ring-opening polymerization using amine-terminated poly(ethyl glycol) as the macroinitiator followed by selective deprotection of the benzyl protecting group. The obtained triblock copolymer can be directly dispersed in aqueous solution with hydrophilic PEG, pH-responsive PGA block, and hydrophobic PNOG. We present a systematic study of the influence of pH, molar fraction, and molecular weight on the self-assemblies. It was found that the PEG-b-PGA-b-PNOG triblock tends to form two-dimensional nanodisks and nanosheet-like assemblies. The nanodisk-to-nanosheet transition is highly dependent on the pH and molar fraction despite the different molecular weights. We demonstrate that the dominant driving force of the nanodisks and nanosheets is the hydrophobicity of the PNOG blocks. The obtained bioinspired 2D nanostructures are potential candidates for applications in nanoscience and biomedicine.
Post-polymerization modification of poly(L-glutamic acid) with D -(+)-glucosamine
Perdih, Peter,ebaek, Sao,Moir, Alenka,agar, Ema
, p. 19751 - 19768 (2014)
Carboxyl functional groups of poly(L-glutamic acid) (PGlu) were modified with a D-(+)-glucosamine (GlcN) by amidation using 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM) as a coupling reagent. The coupling reaction was performed in aqueous medium without protection of hydroxyl functional groups of D-(+)-glucosamine. Poly(L-glutamic acid) and GlcN functionalized polyglutamates (P(Glu-GlcN)) were thoroughly characterized by 1D and 2D NMR spectroscopy and SEC-MALS to gain detailed information on their structure, composition and molar mass characteristics. The results reveal successful functionalization with GlcN through the amide bond and also to a minor extent through ester bond formation in position 1 of GlcN. In addition, a ratio between the α- and β-form of glucosamine substituent coupled to polyglutamate repeating units as well as the content of residual dimethoxy triazinyl active ester moiety in the samples were evaluated.
Thermo-responsive peptide-based triblock copolymer hydrogels
Sanchez-Ferrer, Antoni,Kotharangannagari, Venkata Krishna,Ruokolainen, Janne,Mezzenga, Raffaele
, p. 4304 - 4311 (2013)
A series of novel thermo-responsive peptide-based triblock copolymers, poly(l-glutamic acid)-b-poly(N-isopropylacrylamide)-b-poly(l-glutamic acid) (PLGA-b-PNIPAM-b-PLGA), were successfully synthesized via ring opening polymerization (ROP) of the γ-benzyl l-glutamate derivative (BLG-NCA) using a diamino-terminated PNIPAM as a macroinitiator, followed by de-protection of the benzyl groups. These triblock copolymers form physically crosslinked networks after complexation with a diamino-terminated poly(ethylene oxide) (PEO) in an organic solvent through acid-base proton transfer and successive ionic-bonding confirmed by Fourier transform infrared (FTIR) spectroscopy. The secondary structure of the peptide block, before and after complexation, was confirmed by circular dichroism (CD) experiments, showing an α-helix conformation of the PLGA segments. Swelling experiments on the ionic-bonded networks showed that the water uptake process strongly depends on the temperature and relative humidity conditions. Thus, higher humidity and temperatures below the lower critical solubility temperature (LCST) of the PNIPAM block increase the amount of water absorbed into the network. These swollen ionic complexes contract and reject water when these thermo-responsive peptide-based hydrogels are heated up above their LCST, making them promising for biomedical applications and drug delivery systems.
Synthesis of luminescent 3D microstructures formed by carbon quantum dots and their self-assembly properties
Mazzier,Favaro,Agnoli,Silvestrini,Granozzi,Maggini,Moretto
, p. 6592 - 6595 (2014)
We report in this communication the synthesis of star-shaped carbon quantum dots-(poly-γ-benzyl-l-glutamate) conjugates that self-assemble into microstructures and retain the characteristic emission properties of the native dots. Dots were used either as an initiator to give a daisy-like peptide-polymer structure or as capping agents towards more elaborated hybrid nanostructures. This journal is the Partner Organisations 2014.
PH-sensitive polymeric micelles based on amphiphilic polypeptide as smart drug carriers
Li, Yi,Gao, Guang Hui,Lee, Doo Sung
, p. 4175 - 4182 (2013)
A series of amphiphilic diblock copolymers having poly(ethylene glycol) (PEG) as one block and a polypeptide as the other block were synthesized by ring-opening polymerization using PEG-amine as a macroinitiator. These polymers were characterized by 1H-NMR and gel permeation chromatography. The influence of the substitution ratio of tertiary amine-containing groups on the pH sensitivity of the polymers was investigated in detail. Core/shell-structured micelles were fabricated from these polymers using an organic solvent-free method. pH- and concentration-dependent micellization behaviors were investigated by dynamic light scattering and fluorescence microscopy. Micelles loaded with doxorubicin, selected as a model drug, showed restricted drug release at physiological pH but accelerated drug release at tumor extracellular pH. Collectively, our findings suggest that these pH-sensitive micelles might have great potential for cancer therapy applications.
The behavior of poly(amino acids) containing l -cysteine and their block copolymers with poly(ethylene glycol) on gold surfaces
Obeid, Rodolphe,Armstrong, Tracy,Peng, Xiaoju,Busse, Karsten,Kressler, Joerg,Scholz, Carmen
, p. 248 - 257 (2014)
Poly(ethylene glycol) (PEG) is often used to biocompatibilize surfaces of implantable biomedical devices. Here, block copolymers consisting of PEG and l-cysteine-containing poly(amino acid)s (PAA's) were synthesized as polymeric multianchor systems for the covalent attachment to gold surfaces or surfaces decorated with gold nanoparticles. Amino-terminated PEG was used as macroinitiator in the ring-opening polymerization, (ROP), of respective amino acid N-carboxyanhydrides (NCA's) of l-cysteine (l-Cys), l-glutamate (l-Glu), and l-lysine (l-Lys). The resulting block copolymers formed either diblock copolymers, PEG-b-p(l-Glux-co-l-Cysy) or triblock copolymers, PEG-b-p(l-Glu)x-b-p(l-Cys)y. The monomer feed ratio matches the actual copolymer composition, which, together with high yields and a low polydispersity, indicates that the NCA ROP follows a living mechanism. The l-Cys repeat units act as anchors to the gold surface or the gold nanoparticles and the l-Glu repeat units act as spacers for the reactive l-Cys units. Surface analysis by atomic force microscopy revealed that all block copolymers formed homogenous and pin-hole free surface coatings and the phase separation of mutually immiscible PEG and PAA blocks was observed. A different concept for the biocompatibilization of surfaces was followed when thiol-terminated p(l-Lys) homopolymer was first grafted to the surface and then covalently decorated with HOOC-CH2-PEG-b-p(Bz-l-Glu) polymeric micelles. Copyright
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Blout,Karlson
, p. 941,944 (1956)
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Proximity-Induced Cooperative Polymerization in "hinged" Helical Polypeptides
Chen, Chongyi,Fu, Hailin,Baumgartner, Ryan,Song, Ziyuan,Lin, Yao,Cheng, Jianjun
, p. 8680 - 8683 (2019)
Cooperative interactions and transitions are among the most important strategies utilized by biological systems to regulate a variety of physical and chemical processes. We report herein an auto-accelerated, rapid cooperative polymerization of N-carboxyanhydrides (NCAs) with initiators structurally as simple as linear aliphatic diamines for the synthesis of polypeptides. The polymerization initiated by diamines proceeds via the formation of "hinged" polypeptides, which are two blocks of helical chains connected head-to-head by the diamine molecules in the polymerization solution. The reactions follow a two-stage, cooperative polymerization kinetic; the cooperative interactions between the macrodipoles of the two hinged helical polypeptides dramatically accelerate the polymerization. Compared to the NCA polymerization initiated by the hexylamine (CH3(CH2)5NH2), the chain propagation rate of the NCA polymerization is increased by more than 600 times when initiated by its diamine analogue (1,6-diaminohexane, NH2(CH2)6NH2). This proximity-induced cooperative polymerization showcases the single helix as a remarkable cooperativity-enabling motif in synthetic chemistry.
Quantitative single molecule measurements on the interaction forces of poly(L-glutamic acid) with calcite crystals
Sonnenberg, Lars,Luo, Yufei,Schlaad, Helmut,Seitz, Markus,Coelfen, Helmut,Gaub, Hermann E.
, p. 15364 - 15371 (2007)
The interaction between poly(L-glutamic acid) (PLE) and calcite crystals was studied with AFM-based single molecule force spectroscopy. Block copolymers of poly(ethylene oxide) (PEO) and PLE were synthesized and covalently attached to the tip of an AFM cantilever. In desorption measurements the molecules were allowed to adsorb on the calcite crystal faces and afterward successively desorbed. The corresponding desorption forces were detected with high precision, showing for example a force transition between the two blocks. Because of its importance in the crystallization process in biominerals, the PLE-calcite interaction was investigated as a function of the pH as well as the calcium concentration of the aqueous solution. The sensitivity of the technique was underlined by resolving different interaction forces for calcite (104) and calcite (100).
Surface structure and composition of narrowly-distributed functional polystyrene particles prepared by dispersion polymerization with poly(l-glutamic acid) macromonomer as stabilizer
Itoh, Tomomichi,Tamamitsu, Tetsuo,Shimomoto, Hiroaki,Ihara, Eiji
, p. 183 - 193 (2015)
A novel macromonomer composed of poly(α-l-glutamic acid) was used as a stabilizer for dispersion polymerization of styrene in DMF-water medium with AIBN initiator, giving narrowly-distributed functional polystyrene particles on which the poly(α-l-glutamic acid) was grafted. The resultant particles had 0.54-2.12 μm in size and 0.2-2.6 residue/nm2 in surface density and showed a pH-responsive colloidal behavior associated with a helix-coil transformation of the surface poly(α-l-glutamic acid). Not only the particle size but also the surface density were controlled with macromonomer concentration, macromonomer length, DMF composition, and styrene concentration, while no consistent trend for AIBN concentration was observed. A gel-permeation-chromatography curve of the particles was separated into three components. We tentatively identify the origin of each component and propose a possibility that unstable particles, which were generated even after the growing particles were stabilized, took an important role in particle growth and size distribution of the resultant particles.
Self-assembled micelles composed of doxorubicin conjugated Y-shaped PEG-poly(glutamic acid)2 copolymers via hydrazone linkers
Sui, Bowen,Xu, Hui,Jin, Jian,Gou, Jingxin,Liu, Jingshuo,Tang, Xing,Zhang, Yu,Xu, Jinghua,Zhang, Hongfeng,Jin, Xiangqun
, p. 11915 - 11932 (2014)
In this work, micelles composed of doxorubicin-conjugated Y-shaped copolymers (YMs) linked via an acid-labile linker were constructed. Y-shaped copolymers of mPEG-b-poly(glutamate-hydrazone-doxorubicin)2 and linear copolymers of mPEG-b-poly(glutamate-hydrazone-doxorubicin) were synthesized and characterized. Particle size, size distribution, morphology, drug loading content (DLC) and drug release of the micelles were determined. Alterations in size and DLC of the micelles could be achieved by varying the hydrophobic block lengths. Moreover, at fixed DLCs, YMs showed a smaller diameter than micelles composed of linear copolymers (LMs). Also, all prepared micelles showed sustained release behaviors under physiological conditions over 72 h. DOX loaded in YMs was released more completely, with 30% more drug released in acid. The anti-tumor efficacy of the micelles against HeLa cells was evaluated by MTT assays, and YMs exhibited stronger cytotoxic effects than LMs in a dose- and time-dependent manner. Cellular uptake studied by CLSM indicated that YMs and LMs were readily taken up by HeLa cells. According to the results of this study, doxorubicin-conjugated Y-shaped PEG-(polypeptide)2 copolymers showed advantages over linear copolymers, like assembling into smaller nanoparticles, faster drug release in acid, which may correspond to higher cellular uptake and enhanced extracellular/intracellular drug release, indicating their potential in constructing nano-sized drug delivery systems.
Effect of molecular weight of PGG-paclitaxel conjugates on in vitro and in vivo efficacy
Yang, Danbo,Liu, Xiaoqing,Jiang, Xinguo,Liu, Yun,Ying, Wenbin,Wang, Hai,Bai, Hao,Taylor, Wendy D.,Wang, Yuwei,Clamme, Jean-Pierre,Co, Erick,Chivukula, Padmanabh,Tsang, Kwok Yin,Jin, Yi,Yu, Lei
, p. 124 - 131 (2012)
Polymeric prodrugs are one of the most promising chemotherapeutic agent delivery approaches, displaying unique drug release profiles, serum stability, formulation flexibility, and reduced drug resistance. One of the most important aspects of a polymeric prodrug, albeit a less-extensively studied one, is the polymer's molecular weight, which affects particle formation, drug release and PK/PD profiles, drug stability, and cell uptake; these factors in turn affect the prodrug's maximum tolerated dose and anticancer efficacy. Poly(l-γ-glutamylglutamine) (PGG) is a linear polymer designed to improve the therapeutic index of attached drugs. In this study we selected poly(l-γ-glutamylglutamine)-paclitaxel (PGG-PTX), as a model system for the methodical investigation into the effects of the poly(l-γ- glutamylglutamine) backbone molecular weight on its pharmacological performance. The polymeric prodrug was characterized by NMR, DLS and GPC-MALS, and its anticancer activity in vitro and in vivo was assessed. Herein we present data which provide valuable insight into improving anticancer polymer-based prodrug design and development.
Establishment of a controlled insulin delivery system using a glucose-responsive double-layered nanogel
Lee, DaeYong,Choe, Kibaek,Jeong, YongJun,Yoo, Jisang,Lee, Sung Mun,Park, Ji-Ho,Kim, Pilhan,Kim, Yeu-Chun
, p. 14482 - 14491 (2015)
Glucose-responsive insulin delivery systems have been proposed as a promising alternative to conventional intramuscular administration methods, which causes low patient compliance due to the requirement of multiple administration. In addition, protein-based glucose-responsive systems using glucose oxidase and lectin have not achieved success in clinical trials because of their low biostability and potential cytotoxicity. In order to overcome these issues, the phenylboronic acid (PBA)-derivatives converted to hydrophilic moieties with an elevated glucose level play a key role in controlled insulin delivery systems due to their better biostability and high biocompatibility. In order to endow glucose-responsiveness to insulin delivery carriers using PBA derivatives, a glycol chitosan (GC)/sodium alginate (SA)-poly(L-glutmate-co-N-3-L-glutamylphenylboronic acid) (PGGA) graft polymer double-layered nanogel is synthesized by N-carboxyanhydride (NCA) polymerization and carbodiimide coupling reactions. The GC/SA-PGGA double-layered nanogel controllably releases insulin at diabetic glucose levels in vitro, and shows high biocompatibility, determined by cell viability and a hemolysis assay. Moreover, controlled insulin release at high glucose levels can be accomplished using the GC/SA-PGGA double-layered nanogel in mouse studies. Therefore, the GC/SA-PGGA double-layered nanogel characterized by glucose-sensitivity and superior biocompatibility may act as a potential platform for advanced insulin delivery systems.
One-Step Preparation of pH-Responsive Polymeric Nanogels as Intelligent Drug Delivery Systems for Tumor Therapy
Li, Yi,Bui, Quang Nam,Duy, Le Thai Minh,Yang, Hong Yu,Lee, Doo Sung
, p. 2062 - 2071 (2018)
In this work, pH-responsive polypeptide-based nanogels are reported as potential drug delivery systems. By the formation of pH-sensitive benzoic imine bonds, pH-responsive nanogels are constructed using hydrophilic methoxy poly(ethylene glycol)-b-poly[N-[N-(2-aminoethyl)-2-aminoethyl]-l-glutamate] (MPEG-b-PNLG) and hydrophobic terephthalaldehyde (TPA) as a cross-linker. At pH 7.4, MPEG-b-PNLG nanogels exhibit high stabilities with hydrophobic inner cores, which allow encapsulation of hydrophobic therapeutic agents. Under tumoral acidic environments (pH ～6.4), the cleavage of benzoic imine bonds induces the destruction of MPEG-b-PNLG nanogels and leads to rapid release of their payloads. The formation and pH sensitivity of the nanogels are investigated by dynamic light scattering. These nanogels exhibit excellent stabilities in the presence of salt or against dilution. The globular morphologies of the nanogels are confirmed using transmission electron microscopy. Doxorubicin is used as a model drug to evaluate drug encapsulation and release. Finally, the anticancer activities of the drug-encapsulated nanogels are assessed in vitro.
Biodegradable supramolecular micellesviahost-guest interaction of cyclodextrin-terminated polypeptides and adamantane-terminated polycaprolactones
Pottanam Chali, Sharafudheen,Azhdari, Suna,Galstyan, Anzhela,Gr?schel, André H.,Ravoo, Bart Jan
supporting information, p. 9446 - 9449 (2021/09/22)
Biodegradable supramolecular micelles were prepared exploiting the host-guest interaction of cyclodextrin and adamantane. Cyclodextrin-initiated polypeptides acted as the hydrophilic corona, whereas adamantane-terminated polycaprolactones served as the hydrophobic core.
Synthesis of α-Amino Acid N-Carboxyanhydrides
Laconde, Guillaume,Amblard, Muriel,Martinez, Jean
supporting information, p. 6412 - 6416 (2021/08/30)
A simple phosgene- and halogen-free method for synthesizing α-amino acid N-carboxyanhydrides (NCAs) is described. The reaction between Boc-protected α-amino acids and T3P reagent gave the corresponding NCA derivatives in good yield and purity with no detectable epimerization. The process is safe, is easy-to-operate, and does not require any specific installation. It generates nontoxic, easy to remove byproducts. It can apply to the preparation of NCAs for the on-demand on-site production of either little or large quantities.
