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.
Unimolecular Polypeptide Micelles via Ultrafast Polymerization of N-Carboxyanhydrides
Lv, Shixian,Kim, Hojun,Song, Ziyuan,Feng, Lin,Yang, Yingfeng,Baumgartner, Ryan,Tseng, Kuan-Ying,Dillon, Shen J.,Leal, Cecilia,Yin, Lichen,Cheng, Jianjun
, p. 8570 - 8574 (2020)
Polypeptide micelles are widely used as biocompatible nanoplatforms but often suffer from their poor structural stability. Unimolecular polypeptide micelles can effectively address the structure instability issue, but their synthesis with uniform structure and well-controlled and desired sizes remains challenging. Herein we report the convenient preparation of spherical unimolecular micelles through dendritic polyamine-initiated ultrafast ring-opening polymerization of N-carboxyanhydrides (NCAs). Synthetic polypeptides with exceptionally high molecular weights (up to 85 MDa) and low dispersity (? 1.05) can be readily obtained, which are the biggest synthetic polypeptides ever reported. The degree of polymerization was controlled in a vast range (25-3200), giving access to nearly monodisperse unimolecular micelles with predictable sizes. Many NCA monomers can be polymerized using this ultrafast polymerization method, which enables the incorporation of various structural and functional moieties into the unimolecular micelles. Because of the simplicity of the synthesis and superior control over the structure, the unimolecular polypeptide micelles may find applications in nanomedicine, supermolecular chemistry, and bionanotechnology.
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.
Arborescent polypeptides from γ-benzyl l -glutamic acid
Whitton, Greg,Gauthier, Mario
, p. 5270 - 5279 (2013)
The synthesis of arborescent polymers with poly(γ-benzyl L-glutamate) (PBG) side chains was achieved through successive grafting reactions. The linear PBG building blocks were produced by the ring-opening polymerization of γ-benzyl L-glutamic acid N-carboxyanhydride initiated with n-hexylamine. The polymerization conditions were optimized to minimize the loss of amino chain termini in the reaction. Acidolysis of a fraction of the benzyl groups on a linear PBG substrate and coupling with linear PBG using a carbodiimide/ hydroxybenzotriazole promoter system yielded a comb-branched or generation zero (G0) arborescent PBG. Further partial deprotection and grafting cycles led to arborescent PBG of generations G1 to G3. The solvent used in the coupling reaction had a dramatic influence on the yield of graft polymers of generations G1 and above, dimethylsulfoxide being preferable to N,N-dimethylformamide. This grafting onto scheme yielded well-defined (Mw/Mn ≤ 1.06), high molecular weight arborescent PBG in a few reaction cycles, with number-average molecular weights and branching functionalities reaching over 106 and 290, respectively, for the G3 polymer. α-Helix to coiled conformation transitions were observed from N,N-dimethylformamide to dimethyl sulfoxide solutions, even for the highly branched polymers.
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.
Photoresponsive supramolecular architectures based on polypeptide hybrids
Mazzier, Daniela,Maran, Marco,Polo Perucchin, Omar,Crisma, Marco,Zerbetto, Mirco,Causin, Valerio,Toniolo, Claudio,Moretto, Alessandro
, p. 7272 - 7283 (2014)
Self-aggregation has recently emerged as an efficient tool for the production of well-ordered supramolecular structures at the nanometric scale. In this framework, peptides offer important advantages as building blocks because of their biocompatibility and 3D-structural/functional diversities. The chemical diversity of peptides may be further expanded by use of noncoded amino acids. In the present work, we focused our attention on two known photoswitchable azobenzene-containing α-amino acids and used them as initiators for the reversible modulation of the cis/trans conformational states of two poly(γ-benzyl-l-glutamate)-based hybrid molecules with either C2 or C3 symmetry. The microscopic photoresponsive self-assembly of these compounds was examined in detail. Moreover, these hybrids were exploited in the construction of macroscopic supramolecular architectures via the electrospinning technique. Finally, after appropriate thiol functionalization, we fabricated and characterized dimeric and trimeric gold nanoparticle/polypeptide hybrid 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.
The effect of insulin-loaded linear poly(Ethylene glycol)-brush-like poly(L-lysine) block copolymer on renal ischemia/reperfusion-induced lung injury through downregulating hypoxia-inducible factor
Tong, Fei,Tang, Xiangyuan,Li, Xin,Xia, Wenquan,Liu, Daojun
, p. 1717 - 1730 (2016)
The aim of this study was to observe the therapeutic effect of insulin-loaded linear poly(ethylene glycol)-brush-like poly(l-lysine) block copolymer poly(ethylene glycol)-b-(poly(ethylenediamine l-glutamate)-g-poly(l-lysine)) (PEG-b-(PELG-g-PLL) on renal ischemia/ reperfusion-induced lung injury through downregulating hypoxia-inducible factor (HIF) as compared to free insulin. Sprague Dawley rats were pretreated with 30 U/kg insulin or insulin/ PEG-b-(PELG-g-PLL) complex, and then subjected to 45 minutes of ischemia and 24 hours of reperfusion. The blood and lungs were collected, the level of serum creatinine and blood urea nitrogen were measured, and the dry/wet lung ratios, the activity of superoxide dismutase and myeloperoxidase, the content of methane dicarboxylic aldehyde and tumor necrosis factor-α, and the expression of HIF-1α and vascular endothelial growth factor (VEGF) were measured in pulmonary tissues. Both insulin and insulin/PEG-b-(PELG-g-PLL) preconditioning improved the recovery of renal function, reduced pulmonary oxidative stress injury, restrained inflammatory damage, and downregulated the expression of HIF-1α and VEGF as compared to ischemia/ reperfusion group, while insulin/PEG-b-(PELG-g-PLL) significantly improved this effect.
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.
An unconventional method for purifying the N-carboxyanhydride derivatives of γ-alkyl-L-glutamates
Poche, Drew S.,Moore, Michael J.,Bowles, Jennifer L.
, p. 843 - 854 (1999)
Common impurities in the phosgenation of α-amino acids to produce their N-carboxyanhydride (NCA) derivatives include hydrogen chloride and the hydrochloride salt of the starting amino acid. These impurities can be effectively removed by washing the reaction mixture with water and aqueous bicarbonate at 0 °C prior to isolation of the NCA., despite the well known sensitivity of the NCA to water. The method should be particularly useful for NCA derivatives which are isolated as oils since purifying them by recrystallization or solvent washes is not feasible. This study involved specifically the purification of NCA derivatives from a variety of γ-alkyl- L-glutamates and γ-benzyl-L-glutamate.
