L-phenylalanine Methyl Ester Research Articles

Aspartame, as an artificial sweetener, does not affect renal function and antioxidative states in mice

Background and objectiveAspartame (l-aspartyl l-phenylalanine methyl ester) is an artificial sweetener widely used as a sugar substitute. There are concerns regarding the effects of high aspartame doses on the kidney owing to oxidative stress; however, whether the maximum allowed dose of aspartame in humans affects the kidneys remains unknown. Therefore, in this study, we investigated whether the maximum allowed dose of aspartame in humans affects the kidneys.MethodsIn this study, animals were fed a folate-deficient diet to mimic human aspartame metabolism. Eight-week-old ICR mice were divided into control (CTL), 40 mg/kg/day of aspartame-administered (ASP), folate-deficient diet (FD), and 40 mg/kg/day of aspartame-administered with a folate-deficient diet (FD + ASP) groups. Aspartame was administered orally for eight weeks. Thereafter, we evaluated aspartame’s effect on kidneys via histological analysis.ResultsThere were no differences in serum creatinine and blood urea nitrogen levels between the CTL and ASP groups or between the FD and FD + ASP groups. There was no histological change in the kidneys in any group. The expression of superoxide dismutase and 4-hydroxy-2-nonenal in the kidney did not differ between the CTL and ASP groups or the FD and FD + ASP groups.ConclusionOur findings indicate that the allowed doses of aspartame in humans may not affect kidney function or oxidative states.

Manipulation of Charge Dynamics for Efficient and Bright Blue Perovskite Light-Emitting Diodes with Chiral Ligands.

Perovskite light-emitting diodes (PeLEDs) emerge as a promising class of optoelectronic devices for next-generation displays and lighting technology. However, the performance of blue PeLEDs lags far behind that of their green and red counterparts, including the unachieved trade-off between high efficiency and high luminance, severe efficiency roll-off, and unsatisfactory power efficiency. Here, a multi-functional chiral ligand of L-phenylalanine methyl ester hydrochloride is strategically introduced into quasi-two-dimensional perovskites, which can effectively passivate defects, modulate the phase distribution, improve photoluminescence quantum yield, guarantee high-quality film morphology, and enhance charge transport. Furthermore, ladder-like hole transport layers are established, boosting charge injection and balance. The resultant sky-blue PeLEDs (the photoluminescence peak is 493nm, and the electroluminescence peak is 497nm) exhibit an external quantum efficiency of 12.43% at 1000cd m-2 and a record power efficiency of 18.42lm W-1 , rendering that the performance is among the best blue PeLEDs. This article is protected by copyright. All rights reserved.

Three New Compounds from Delphinium kamaonense Hunth and Their in Vitro Cytotoxic and Potential Antioxidant Activities.

A new amide (1), two new phenylpropanoid derivatives (2, 3), along with three new natural products, including three nitrogen chirality compounds, N-(3-methoxy-1,3-dioxopropyl)-D-phenylalanine methyl ester (4), N-(3-methoxy-1,3-dioxopropyl)-L-phenylalanine methyl ester (5), and N-acetyl-L-phenylalanine methyl ester (6), as well as dimethyl (2R,3R)-2-hydroxy-3-(((E)-3-(4-hydroxyphenyl)acryloyl)oxy)succinate (7) and dimethyl (S,E)-2-((3-(4-hydroxy-3-methoxyphenyl)acryloyl)oxy)succinate (8) were isolated from Delphinium kamaonense Hunth. Their structures were elucidated by extensive analysis of 1D and 2D NMR, and HR-ESI-MS experiments, and the absolute configurations were determined by comparative analysis of specific optical rotation. Compound 1 exhibited a moderate cytotoxicity effect against Hep-3B cancer cell lines (IC50 41.39±0.13 μM) and an excellent antioxidant activity (IC50 0.527±0.06 μM in ABTS assay, and 1.235±0.09 μM in DPPH assay, respectively), which was superior to vitamin C in ABTS (IC50 1.670±0.07 μM) and DPPH (IC50 19.10±0.40 μM) methods.

Short-step Synthesis of Cordytakaoamide B and Cordycepamide C via Intramolecular Regioselective Oxidation-Lactone Formation

The ortho-tyrosinol derivative, as a key synthetic intermediate for alkaloidal metabolites of Cordyceps, was synthesized from L-phenylalanine methyl ester via condensation with crotonic acid and oxidative intramolecular lactone formation by using phenyliodine(III) bis(trifluoroacetate). Subsequent elongation of the side chain involving a cross-metathesis reaction and deprotection yielded cordytakaoamide B and cordycepamide C in notably few synthetic steps. Furthermore, the S-configurations at the C-2 position of both cordytakaoamide B and cordycepamide C were confirmed by comparison with the sign of the optical rotation of the synthetic sample.

Preparation and Characterization of Water-Insoluble Gardenia Blue Pigment.

Based on molecular simulations, the synthetic route of water-insoluble gardenia blue pigment was prepared by the reaction of genipin and L-Phenylalanine methyl ester hydrochloride. A highly purified pigment was obtained after extraction by chloroform and purification by silica gel column chromatography, and the value of color is up to 288. A study on the structural characteristics of the pigment was implemented with a scanning electron microscope, ultraviolet-visible spectrophotometer, Fourier transform infrared spectrometer, X-ray photoelectron spectrometer, and quatropde-time of flight mass spectrometer. The results showed that the surface of the pigment was largely smooth and spherical; The λmax was 607 nm, and the main functional groups include O-C=O, C=O, C-N, C=C, OH, and benzene ring; We detrained six different molecular weight and chemical structures of pigments and speculated the particular structures and formation mechanisms of three kinds of pigment, whose molecular weights are 690.1156, 720.1226, and 708.1246 Da, respectively. The pigment was only able to be dissolved in ethanol, methanol, acetone, ethyl acetate, and other strong polar organic solvents, but was not able to be dissolved in water, ethyl ether, petroleum ether, and other weak polar organic solvents. In terms of light and thermal stabilities, water-insoluble gardenia blue pigment is significantly better than water-soluble gardenia blue pigment (p < 0.05). When it is under direct light for 7 days or incubated at 80–120 °C for 24 h, the pigment residual rates were 74.90, 95.26, 88.27, and 87.72%, respectively.

Ionic liquids derived from α-amino acid ester salts as potent green corrosion inhibitors for mild steel in 1M HCl

In 1 M HCl solution, three selected amino acid ester salt based ionic liquids ([AAE][Sac] ILs), namely L-Phenyl Alanine methyl ester saccharinate ([PheME][Sac]), L-Leucine methyl ester saccharinate ([LeuME][Sac]), and L-Alanine methyl ester saccharinate ([AlaME][Sac]) under static conditions were examined as potent green corrosion inhibitors for mild steel by means of electrochemical measurements, weight loss, FT-IR spectroscopy, contact angle measurement, UV–vis spectroscopy, SEM/EDAX study, quantum chemical calculations and Monte Carlo (MC) simulation studies. 1H NMR, and FTIR spectroscopy has confirmed the structure of obtained ILs. The investigations were done in the temperature range of 303–353 K. [AAE][Sac] ILs are assessed as an efficient steel corrosion inhibitors in 1 M HCl up to 333 K but have less inhibiting properties above 333 K i.e., 343 and 353 K. Among the [AAE][Sac] ILs analysed, [PheME][Sac] showed the greatest inhibition efficiency and obey the order as: [PheME][Sac] > [LeuME][Sac] > [AlaME][Sac]. Polarization measurements showed all the [AAE][Sac] ILs tested to be mixed-type inhibitors. The adsorption of the examined [AAE][Sac] ILs obeyed the Langmuir adsorption isotherm perfectly. The theoretical descriptors provided by quantum chemical calculations and advanced MC simulation also reinforced the experimental conclusions adequately.

Synthesis and characterization of novel amphiphilic biocompatible block-copolymers of poly(N-isopropylacrylamide)-b-poly(l-phenylalanine methyl ester) by RAFT polymerization

The synthesis of amphiphilic block-copolymers of poly(N-isopropylacrylamide) (PNIPAM) and poly(N-acryloyl-l-phenylalanine methyl ester) (PNALPA) by RAFT polymerization is reported. The polymers were characterized by proton NMR (1H NMR), gel permeation chromatography (GPC), powder X-ray diffraction (XRD), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA) to understand their structure-property relationships. All synthesized polymers show pH triggered release at acidic (pH 5) and biological pH (pH 7.4). Critical micellar concentration also varied systematically depending on the amphiphilic nature of the polymers. Biocompatibilities of the polymers are also determined to check their suitability for biomedical applications.

Synthesis and Anti-Inflammatory and Antiulcer Activity of a Glycyrrhizic Acid Conjugate with L-Phenylalanine Methyl Ester

A conjugate of glycyrrhizic acid (GA) with L-phenylalanine methyl ester was synthesized using N-hydroxysuccinimide and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide. Chemical modification of GA via addition of L-phenylalanine methyl ester moieties in the carbohydrate part of the glycoside was shown to form a marginally toxic compound with high anti-inflammatory activity in carrageenan- and formalin-induced mouse inflammation models and with pronounced antiulcer activity in rats. This was a significant advantage of this compound over known anti-inflammatory drugs.

Enhancing Membrane-Disruptive Activity via Hydrophobic Phenylalanine and Lysine Tethered to Poly(aspartic acid).

Amphiphilic polymers with pH-responsive abilities have been widely used as carriers for intracellular delivery of bioactive substances, while their membrane-disruptive activity exerted on cells is a critical characteristic that determines delivery efficiency. Herein, we present a novel method to prepare amphiphilic and pH-responsive polymers by chemically tethering l-phenylalanine methyl ester and followed by Nε-carbobenzyloxy-l-lysine benzyl ester to the side carboxylic acid groups of poly(aspartic acid). The obtained phenylalanine- and lysine-grafted polymer (PAsp- g-Phe)- g-Lys demonstrated enhanced membrane-disruptive activity at pH 7.4 in comparison with that of PAsp- g-Phe. Moreover, the pH-responsive behavior of the grafted polymers caused by the significantly intensified hydrophobicity could be modulated by the tethered amount of hydrophobic amino acids with phenyl groups. The prepared amphiphilic (PAsp- g-Phe)- g-Lys could facilitate entry of calcein into NIH/3T3 and HeLa cells at physiological pH values, possibly due to local chemical destabilization of cell membranes by the interaction between the polymer and membrane bilayers. Therefore, we have provided a feasible approach to prepare pH-responsive polymers with enhanced membrane-disruptive activity, and the phenylalanine- and lysine-grafted polymers could be a potential candidate for intracellular delivery of bioactive molecules in biomedical applications.

An Aminocaprolactam Racemase from Ochrobactrum anthropi with Promiscuous Amino Acid Ester Racemase Activity.

The kinetic resolution of amino acid esters (AAEs) is a useful synthetic strategy for the preparation of single-enantiomer amino acids. The development of an enzymatic dynamic kinetic resolution (DKR) process for AAEs, which would give a theoretical yield of 100 % of the enantiopure product, would require an amino acid ester racemase (AAER); however, no such enzyme has been described. We have identified low AAER activity of 15 U mg-1 in a homologue of a PLP-dependent α-amino ϵ-caprolactam racemase (ACLR) from Ochrobactrum anthropi. We have determined the structure of this enzyme, OaACLR, to a resolution of 1.87 Å and, by using structure-guided saturation mutagenesis, in combination with a colorimetric screen for AAER activity, we have identified a mutant, L293C, in which the promiscuous AAER activity of this enzyme towards l-phenylalanine methyl ester is improved 3.7-fold.

Poly-N-acryloyl-(l-phenylalanine methyl ester) hollow core nanocapsules facilitate sustained delivery of immunomodulatory drugs and exhibit adjuvant properties.

Polymeric hollow nanocapsules have attracted significant research attention as novel drug carriers and their preparation is of particular concern owing to the feasibility to encapsulate a broad range of drug molecules. This work presents for the first time the synthesis and development of novel poly-N-acryloyl l-phenylalanine methyl ester hollow core nanocapsules (NAPA-HPNs) of avg. size ca. 100-150 nm by the mini-emulsion technique. NAPA-HPNs are biocompatible and capable of encapsulating sodium nitroprusside (SNP) at a rate of ∼1.3 μM per mg of capsules. These NAPA-HPNs + SNP nano-formulations maintained homeostasis of macrophages which carry and facilitate the action of various drug molecules used against various diseases. These NAPA-HPNs also facilitate the prolonged release of a low level of nitric oxide (NO) and enhance the metabolic activities of pro-inflammatory macrophages, which are important for the action of various drugs in body fluids. NAPA-HPN mediated skewing of naïve macrophages toward the M1 phenotype potentially demonstrates its adjuvant action on the innate immune system. These results potentially suggested that NAPA-HPNs can serve both as a carrier of drugs as well as an adjuvant for the immune system. Thus, these nanocapsules could be used for the effective management of various infectious or tumor diseases where immune-stimulation is paramount for treatment.

Chemical Modification of Laccase from Aspergillus oryzae and its Application in OCC Pulp

Laccase activity and stability were improved and modified through the interaction between laccase amino acid residues (e.g., amino groups (-NH2) and carboxyl groups (-COOH)) and the chemical reagents thiourea dioxide (TDO) and L-phenylalanine methyl ester hydrochloride (L-PME). Compared with the control sample, the activity of the laccase modified with these chemical reagents was increased by 209% and 50%, respectively. The stability of the laccase modified with L-PME increased by 56.9%. However, the laccase modified with TDO only improved slightly. It was clear that reagent L-PME was more efficacious than TDO. The paper formed with addition of L-PME-modified laccase exhibited better performance in terms of tensile strength, bursting strength, and tear strength, which increased by 13%, 10%, 9%, respectively, compared with the paper formed with unmodified laccase.

A comparative study of papain and bromelain in enzymatic oligomerization of l-Phe methyl ester in aqueous environment

In this study, we developed an efficient approach for hydrophobic amino acids polymerization in aqueous solution. We compared the catalysis efficiency of papain and bromelain in catalyzing l-phenylalanine methyl ester (l-Phe-Me) for oligomer peptides synthesis. A set of reaction conditions (such as protease type, reaction temperature, time, and pH) have been tested for the polymerization reaction with papain and bromelain, respectively. Moreover, the resultant oligomers were analyzed through 1HNMR and MALDI-TOF. The results indicated that the average degree of polymerization (DP) reached the highest value (6.74) when papain was used for l-Phe-Me polymerization in phosphate buffer (0.2M, pH 8) at 40°C for three hours. At 50°C, the DP reached 6.62 with a yield of 72.9% when papain as the catalyst. Its yield and DP were 4.50 and 1.27 folds higher than those of the oligo- peptides synthesized by bromelain. Moreover, we found the DP and the yield of oligo(l-Phe) can be enhanced with higher reaction temperature and longer reaction time. In summary, papain presents better catalytic properties compared with bromelain for l-Phe polymerization in terms of DP and yield. Oligomerization catalyzed by papain at high temperature presents a potent procedure for the synthesis of biologically active oligo(l-Phe) peptides.

High-effective approach from amino acid esters to chiral amino alcohols over Cu/ZnO/Al2O3 catalyst and its catalytic reaction mechanism.

Developing the high-efficient and green synthetic method for chiral amino alcohols is an intriguing target. We have developed the Mg2+-doped Cu/ZnO/Al2O3 catalyst for hydrogenation of L-phenylalanine methyl ester to chiral L-phenylalaninol without racemization. The effect of different L-phenylalanine esters on this title reaction was studied, verifying that Cu/ZnO/Al2O3 is an excellent catalyst for the hydrogenation of amino acid esters to chiral amino alcohols. DFT calculation was used to study the adsorption of substrate on the catalyst, and showed that the substrate adsorbs on the surface active sites mainly by amino group (-NH2) absorbed on Al2O3, and carbonyl (C=O) and alkoxy (RO-) group oxygen absorbed on the boundary of Cu and Al2O3. This catalytic hydrogenation undergoes the formation of a hemiacetal intermediate and the cleavage of the C–O bond (rate-determining step) by reacting with dissociated H to obtain amino aldehyde and methanol ad-species. The former is further hydrogenated to amino alcohols, and the latter desorbs from the catalyst surface.

Synthesis of 3-trimethylsiloxy-1-(furan-3-yl)butadiene and its reactions with dienophiles

3-Trimethylsilyloxy-1-(furan-3-yl)butadiene was synthesized and studied in reactions with 2,2-dimethyl-5-methylidene-1,3-dioxane-4,6-diones, 5-methylenepyrimidine-2,4,6-triones, as well as with imines. Reactions with dienophiles containing an exo-methylene double bond in the presence of L-proline occurred regio- and stereoselectively with the formation of 7-(furan-3-yl)spiro[5,5]undecane-1,5,9-triones or 7-(furan-3-yl)-2,4-diazaspiro[5.5]undecane-1,3,5,9-tetraones. The reaction of diene with methylene imine, obtained from L-phenylalanine methyl ester and formaldehyde, in the presence of Lewis acids led to the formation of 2-(furan-3-yl)piperidin-4-one or the product of ene reaction, methyl (2S)-2-{[(4E)-5-(furan-3-yl)-3-oxopent-4-en-1-yl]amino}-3-phenylpropanoate. The structures of three compounds were confirmed by X-ray structural analysis.

Hemicucurbiturils as receptors in extraction and transport of some amino acids

The molecular recognition properties of hemicucurbit[6]uril (HemiCB[6]) and hemicucurbit[12]uril (HemiCB[12]) towards a series of amino acid native and methyl esters (L-phenylalanine, L-leucine, L-valine, L-cysteine, L-tryptophan, L-isoleucine, L-phenylalanine methyl ester hydrochloride (L-PheOMe), L-tyrosine methyl ester hydrochloride (L-TyrOMe), L-valine methyl ester hydrochloride (L-ValOMe), L-leucine methyl ester hydrochloride (L-LeuOMe), L-serine methyl ester hydrochloride (L-SerOMe) and L-cysteine methyl ester hydrochloride (L-CysOMe) were investigated. In this respect, by means of liquid–liquid extraction, a series of amino acid native and methyl esters were extracted from an aqueous phase (pH = 5.5) into a chloroform phase as ion pairs in the presence of tropaeolin 00 as counterion. Based on results obtained in extraction experiments, the active transport assisted by pH gradient of amino acids as ion pairs through chloroform liquid membrane employing HemiCB[6] as carrier was performed. Both receptors used in experiments exhibited extractability towards amino acids under study. From the results obtained, one can observed the good affinity of both receptors, hemiCB[6, 12], towards hydrophobic amino acids (L-PheOMe, L-LeuOMe and L-ValOMe)). It was emphasised that the structure of hemicucurbiturils and amino acids together with the anion nature, and pH have influenced the experimental results.

L-Phenylalanine methyl ester hydrochloride as a green corrosion inhibitor for mild steel in hydrochloric acid solution and the effect of surfactant additive

Structure ofl-phenylalanine methyl ester hydrochloride.

Synthesis of chiral linear and macrocyclic candidates: VI. Synthesis and antibacterial activity of some macrocyclic tripeptides and linear dipeptide Schiff bases

A series of macrocyclic tripeptides and linear dipeptide Schiff base derivatives has been synthesized using pyridine-3,5-dicarboxylic acid and L-phenyalanine methyl ester as starting materials. Treatment of pyridine-3,5-dicarbonyl dichloride with L-phenylalanine methyl ester gave N,N′-(pyridine-3,5-diyldicarbonyl)bis(L-phenyalanine methyl ester) which was hydrolyzed with 1N sodium hydroxide to the corresponding bis-acid, and the latter was cyclized with diamino acids to afford macrocyclic tripeptide derivatives. The reaction of the bis ester with hydrazine hydrate gave bis-hydrazide, which was condensed with aldehydes to obtain the corresponding Schiff base derivatives. The structures of the newly synthesized compounds were confirmed by IR, 1H and 13C NMR, and MS spectral data and elemental analyses. The antimicrobial activities of some of the newly synthesized compounds were comparable with that of Streptomycin used as control.

Sugar-based novel chiral macrocycles for inclusion applications and chiral recognition

A convergent template assisted synthesis of sugar-based chiral macrocycles has been achieved. The host–guest inclusion studies have revealed significant interactions of the synthesized macrocycle with primary over secondary ammonium salt. The chiral macrocyle also discriminates between D- and L-phenylalanine methyl ester hydrochlorides as revealed by 1H NMR spectral studies on the mixture of the host and the guest molecules.

Synthesis and crystal structure of imidazole containing amide as a turn on fluorescent probe for nickel ion in aqueous media. An experimental and theoretical investigation

Imidazole containing amide fluorescence probe (PAIC) for Ni2+ was designed and successfully synthesized in good yield by reaction between 1-methyl-1H-imidazole-2-carboxylic acid and l-phenylalanine methyl ester. The probe was characterized by FTIR, 1H NMR, ESI-MS, UV–vis and fluorescence spectroscopy. Single crystal XRD analysis reveals that PAIC crystallizes in a monoclinic crystal lattice system with the space group of P21/n. Chemosensor property of PAIC was tested against different metal ions by UV–vis and fluorescent techniques in aqueous medium. Test results show that PAIC has high selectivity for Ni2+ compared to other metal ions (Na+, K+, Ca2+, Ag+, Co2+, Cu2+, Fe2+, Fe3+, Hg2+, Mn2+, Zn2+ and Pb2+). Time-dependent density functional theory (TD-DFT) and configuration interaction singles (CIS) calculations were carried out to understand the sensing mechanism. The practical applicability of PAIC was tested in real water samples.