14825-82-2Relevant articles and documents
Dual-responsive star-shaped polypeptides for drug delivery
Wang, Wenlong,Zhang, Liang,Liu, Mengtao,Le, Yuan,Lv, Shanshan,Wang, Jiexin,Chen, Jian-Feng
, p. 6368 - 6377 (2016)
Core cross-linked star-shaped polypeptides based on poly(l-glutamic acid)-poly(l-phenylalanine-co-l-cystine) copolymer have been successfully synthesized and thoroughly characterized. The star polypeptides can self-assemble to form 50 nm micelles in aqueous medium, which respond rapidly to both pH change within the physiologically relevant pH range and a reduction environment mimicking the intracellular space. Water-soluble doxorubicin hydrochloride and hydrophobic resveratrol are loaded into the star polypeptides micelles through electrostatic and hydrophobic interactions respectively. The drug loading content can be controlled by tuning the composition of the star polypeptides. The in vitro release studies indicate dual sensitivity enabled rapid drug release at pH 5.5 and 10 mM dithiothreitol (DTT), mimicking the intracellular environment. Furthermore, the star polypeptides are biocompatible and interact well with cells in vitro. Confocal fluorescence microscopy and flow cytometry assays show these star polypeptides can be quickly internalized and effectively deliver the drugs into HeLa cells to inhibit cell growth.
Investigation of N-carbamoylamino acid nitrosation by {NO + O2 in the solid-gas phase. Effects of NOx speciation and kinetic evidence for a multiple-stage process
Lagrille, Olivier,Taillades, Jacques,Boiteau, Laurent,Commeyras, Auguste
, p. 271 - 284 (2007)
Nitrosation of N-carbamoylamino acids (CAA) by gaseous NO + O2, an interesting synthetic pathway to amino acid N-carboxyanhydrides (NCA), alternative to the phosgene route, was investigated on N-carbamoyl-valine either in acetonitrile suspension or solventless conditions, and compared to the classical nitrosating system NaNO2 + CF3COOH (TFA), the latter being quite less efficient in terms of either rate, stoichiometric demand, or further tractability of the product. The rate and efficiency of the NO + O2 reaction mainly depends on the O2/NO ratio. Evaluation of the contribution of various nitrosating species (N 2O3, N2O4, HNO2) through stoichiometric balance showed the reaction to be effected mostly by N 2O3 for O2/NO ratios below 0.3, and by N 2O4 for O2/NO ratios above 0.4. The relative contribution of (subsequently formed) HNO2 always remains minor. Differential scanning calorimetry (DSC) monitoring of the reaction in the solid phase by either HNO2 (from NaNO2 + TFA), gaseous N 2O4 or gaseous N2O3, provides the associated rate constants (ca. 0.1, 2 and 108 s-1 at 25°C, respectively), showing that N2O3 is by far the most reactive of these nitrosating species. From the DSC measurement, the latent heat of fusion of N2O3, 2.74 kJ ·mol-1 at -105 °C is also obtained for the first time. The kinetics was investigated under solventless conditions at 0°C, by either quenching experiments or less tedious, rough calorimetric techniques. Auto-accelerated, parabolic-shaped kinetics was observed in the first half of the reaction course, together with substantial heat release (temperature increase of ca. 20°C within 1-2 min in a 20-mg sample), followed by pseudo-zero-order kinetics after a sudden, important decrease in apparent rate. This kinetic break is possibly due to the transition between the initial solid-gas system and a solid-liquid-gas system resulting from water formation. Overall rate constants increased with parameters such as the specific surface of the solid, the O 2/NO ratio, or the presence of moisture (or equivalently the hydrophilicity of the involved CAA), however without precise relationship, while the last two parameters may directly correlate to the increasing acidity of the medium. Copyright
Biodegradable hybrid polymer micelles for combination drug therapy in ovarian cancer
Desale, Swapnil S.,Cohen, Samuel M.,Zhao, Yi,Kabanov, Alexander V.,Bronich, Tatiana K.
, p. 339 - 348 (2013)
The co-delivery of drug combination at a controlled ratio via the same vehicle to the cancer cells is offering the advantages such as spatial-temporal synchronization of drug exposure, synergistic therapeutic effects and increased therapeutic potency. In an attempt to develop such multidrug vehicle this work focuses on functional biodegradable and biocompatible polypeptide-based polymeric micelles. Triblock copolymers containing the blocks of ethylene glycol, glutamic acid and phenylalanine (PEG-PGlu-PPhe) were successfully synthesized via NCA-based ring-opening copolymerization and their composition was confirmed by 1H NMR. Self-assembly behavior of PEG-PGlu 90-PPhe25 was utilized for the synthesis of hybrid micelles with PPhe hydrophobic core, cross-linked ionic PGlu intermediate shell layer, and PEG corona. Cross-linked (cl) micelles were about 90 nm in diameter (ξ-potential = -20 mV), uniform (narrow size distribution), and exhibited nanogels-like behavior. Degradation of cl-micelles was observed in the presence of proteolytic enzymes (cathepsin B). The resulting cl-micelles can incorporate the combination of drugs with very different physical properties such as cisplatin (15 w/w% loading) and paclitaxel (9 w/w% loading). Binary drug combination in cl-micelles exhibited synergistic cytotoxicity against human ovarian A2780 cancer cells and exerted a superior antitumor activity by comparison to individual drug-loaded micelles or free cisplatin in cancer xenograft model in vivo. Tunable composition and stability of these hybrid biodegradable micelles provide platform for drug combination delivery in a broad range of cancers.
Synthesis of novel copolymer: Poly(p-dioxanone-co-l-phenylalanine)
Wang, Bing,Ma, Chi,Xiong, Zuo-Chun,Xiong, Cheng-Dong,Zhou, Quan-Hua,Chen, Dong-Liang
, p. 392 - 396 (2013)
In order to expand the application of poly(p-dioxanone) or PPDO in biomedical area, a series of novel copolymers were synthesized successfully by one-step, melted copolymerization of p-dioxanone (PDO) and l-phenylalanine N-carboxyanhydride (l-Phe-NCA) monomers. With the in-feed molar ratio of l-Phe-NCA/PDO equal to 1/20, the conversions of the two kinds of monomers were calculated from 1H NMR. The average molecular weight and polydispersity of the copolymer increase with the increasing reaction time and catalyst concentration. However, the conversions of the two kinds of monomers did not change with the reaction conditions. A three-step mechanism is presented and proved by high resolution 1H NMR and IR spectrums.
Self-assembled spin-labeled nanoparticles based on poly(amino acids)
Hubina,Pogodaev,Sharoyko,Vlakh,Tennikova
, p. 173 - 180 (2016)
The development of detectable nanoparticles for controlled drug delivery systems has tremendous practical importance regarding the monitoring of drug pathway in organism. Self-assembly amphiphilic block-copolymer poly(l-glutamic acid)-b-poly(l-phenylalanine) (pGlu-b-pPhe) was chosen for the preparation of discussed nanoparticles. The synthesis of blocks was carried out using ring-opening polymerization (ROP) of N-carboxyanhydrides of mentioned amino acids. To introduce the spin label at C-terminal position of hydrophilic block, (4-amino-2,2,6,6-tetramethylpiperidin-1-yl)oxyl (4-amino-TEMPO) was applied as ROP initiator and the polymerization of hydrophobic block was carried out with previously synthesized macroinitiator. The results obtained by transmission electron microscopy clearly showed that TEMPO-pGlu-b-pPhe polymer was really capable to self-assembling in aqueous solutions followed by polymersome formation. The mean size of nanoparticles was increased in a range of TEMPO-pGlu43-b-pPhe12 43-b-pPhe29 43-b-pPhe49 as 60 200 280 nm, respectively. EPR spectroscopy of the solutions of spin-labeled homopolymer TEMPO-p-γ-Glu(Bzl), block copolymers TEMPO-p-γ-Glu(Bzl)-b-pPhe and suspension of polymersomes formed from TEMPO-p-Glu-b-pPhe was performed and the results were compared. It was proved that in the case of nanoparticles EPR detectable spin labels are located on polymersome surface. The experiments in cell culture demonstrated the absence of cytotoxicity of labeled nanoparticles. Additionally, it was shown that TEMPO-label can be detected inside the cell by EPR method.
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.
METHOD FOR PRODUCING AMINO ACID-N-CARBOXYLIC ACID ANHYDRIDE
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Paragraph 0063-0065; 0072, (2020/08/07)
PROBLEM TO BE SOLVED: To provide: a method for safely and efficiently producing amino acid-N-carboxylic acid anhydride; and a method for producing peptide by using the obtained amino acid-N-carboxylic acid anhydride. SOLUTION: The method for producing an amino acid-N-carboxylic acid anhydride according to the present invention is characterized in that the amino acid-N-carboxylic acid anhydride is represented by the following formula (II), and a step of irradiating a composition containing a halogenated methane and an amino acid compound represented by the following formula (I) with high energy light in the presence of oxygen is included. [In the formula, R1 represents an amino acid side chain group in which the reactive group is protected, and R2 represents H or the like.]. SELECTED DRAWING: None COPYRIGHT: (C)2020,JPOandINPIT
Formamide catalyzed activation of carboxylic acids-versatile and cost-efficient amidation and esterification
Huy, Peter H.,Mbouhom, Christelle
, p. 7399 - 7406 (2019/08/20)
A novel, broadly applicable method for amide C-N and ester C-O bond formation is presented based on formylpyrrolidine (FPyr) as a Lewis base catalyst. Herein, trichlorotriazine (TCT), which is the most cost-efficient reagent for OH-group activation, was employed in amounts of ≤40 mol% with respect to the starting material (100 mol%). The new approach is distinguished by excellent cost-efficiency, waste-balance (E-factor down to 3) and scalability (up to >80 g). Moreover, high levels of functional group compatibility, which includes acid-labile acetals and silyl ethers, are demonstrated and even peptide C-N bonds can be formed. In comparison to reported amidation procedures using TCT, yields are considerably improved (for instance from 26 to 91%) and esterification is facilitated for the first time in synthetically useful yields. These significant enhancements are rationalized by activation by means of acid chlorides instead of less electrophilic acid anhydride intermediates.
