Na＋-丙氨酸二肽络合离子结构的密度泛函理论研究

运用密度泛函理论B3LYP方法在6-311＋＋G**基组水平下研究了Na^＋与丙氨酸二肽(AD)分子结合形成的6种Na^＋-AD 络合离子, 其中包括2种双齿结构和4种单齿结构. 考察了6种Na^＋-AD络合离子的相对稳定性, 分析了丙氨酸二肽分子与Na^＋作用过程中分子骨架Ramachandran角f和Ψ以及分子内氢键的变化.     

Three-component catalytic method for synthesis of α-amino phosphonates with the use of α-amino acids as amine component

Interaction of aliphatic and aromatic aldehydes and ketones with optically active L-α-amino acids or their esters in the three-component catalytic one-pot synthesis of α-aminophosphonates was studied. The corresponding α-amino phosphonates are formed in high yields as mixtures of diastereomers. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 768–774, April, 2007.     

荧光法研究Ge—132对苯丙氨酸Maillard反应的抑制作用

哺乳动物体内氨基酸及蛋白质的非酶糖化反应（Ｍａｉｌａｒｄ反应）与糖尿病及其并发症的关系已引起广泛关注［１］，β－羧乙基锗倍半氧化物（Ｇｅ－１３２）具有预防糖尿病和调节糖代谢的作用［２］，研究Ｇｅ－１３２对Ｍａｉｌａｒｄ反应的抑制作用对于开发防治糖尿病...     

Astragalus membranaceus ultrafine powder alleviates hyperuricemia by regulating the gut microbiome and reversing bile acid and adrenal hormone biosynthesis dysregulation

Ethnopharmacological relevanceMetabolic syndrome is closely related to the intestinal microbiota and disturbances in the host metabolome. Hyperuricemia (HUA), a manifestation of metabolic syndrome, can induce various cardiovascular diseases and gout, seriously affecting a patient’s quality of life. Astragalus membranaceus has a long history as a commonly used traditional Chinese medicine to treat kidney disease in China and East Asia.Materials and methodsWe compared the therapeutic effect of benzbromarone and two different doses Astragalus membranaceus ultrafine powder (AMUP) in rats with HUA. Ultra-performance liquid chromatography-mass spectrometer was used to analyze the AMUP metabolism in the plasma, urine, and feces. Further, 16S ribosome RNA sequencing and feces metabolomic were performed to capture the variation of the gut microbiota and metabolites changes before and after drug administration.ResultsAMUP had a notable impact on reducing blood uric acid levels while protecting the liver and kidney. Drug metabolism analysis demonstrated that effective constituent flavonoids are distributed in the blood, whereas saponins remain in the intestine. Gut microbiota analysis showed that low-dose AMUP ameliorated HUA-induced gut dysbiosis by reducing the abundance of harmful bacteria and increasing that of some beneficial bacteria with anti-inflammatory properties, such as Clostridia, Lachnospiraceae, and Muribaculaceae. In addition, HUA-induced changes in metabolite contents in bile acid and adrenal hormone biosynthesis pathways were restored after treatment with AMUP.ConclusionLow-dose AMUP exerts remarkable therapeutic effects on HUA by regulating the gut microbiome and mediating gut metabolism pathways associated with uric acid excretion.     

Synthesis of alanine and leucine by reductive amination of 2-oxoic acid with combination of hydrogenase and dehydrogenase

Alanine synthesis by reductive amination of pyruvate was performed by the combination of NADH regeneration system and alanine dehydrogenase (AlaDH). The conversion of pyruvate to alanine was 99% after 1 h. Leucine synthesis was also carried out by the combination of NADH regeneration system and leucine dehydrogenase (LeuDH). The conversion of 4-methyl-2-oxovalerate to leucine was 60% after 1.5 h.     

5-(4-丙氨酸丁氧苯基)-10,15,20-三苯基卟啉及其配合物的合成和性质

本文首次合成了一种新型的单取代的丙氨酸四苯基卟啉，５－（４－丙氨酸丁氧苯基）－１０，１５，２０－三苯基卟啉（Ｈ２Ｌ），及其Ｃｏ（Ⅱ）、Ｃｕ（Ⅱ）、Ｚｎ（Ⅱ）配合物（ＣｏＬ、ＣｕＬ、ＺｎＬ），用元素分析、电子光谱、红外光谱、荧光光谱和激光拉曼光谱进行表征。研究了ＭＬ存在下，用氧气氧化芳醛的过程，测定了反应体系的吸氧动力学曲线，研究了氧化过程金属卟啉可见光谱变化以及底物和金属卟啉浓度对反应的影响。结果表明，ＣｏＬ能加速芳醛氧化反应，最大吸氧速率随ＣｏＬ浓度的增加而增大，但反应诱导期随ＣｏＬ浓度增大而延长。     

A structure-based design approach for the identification of novel inhibitors: application to an alanine racemase

We report a new structure-based strategy for the identification of novel inhibitors. This approach has been applied to Bacillus stearothermophilus alanine racemase (AlaR), an enzyme implicated in the biosynthesis of the bacterial cell wall. The enzyme catalyzes the racemization of l- and d-alanine using pyridoxal 5-phosphate (PLP) as a cofactor. The restriction of AlaR to bacteria and some fungi and the absolute requirement for d-alanine in peptidoglycan biosynthesis make alanine racemase a suitable target for drug design. Unfortunately, known inhibitors of alanine racemase are not specific and inhibit the activity of other PLP-dependent enzymes, leading to neurological and other side effects.This article describes the development of a receptor-based pharmacophore model for AlaR, taking into account receptor flexibility (i.e. a `dynamic' pharmacophore model). In order to accomplish this, molecular dynamics (MD) simulations were performed on the full AlaR dimer from Bacillus stearothermophilus (PDB entry, 1sft) with a d-alanine molecule in one active site and the non-covalent inhibitor, propionate, in the second active site of this homodimer. The basic strategy followed in this study was to utilize conformations of the protein obtained during MD simulations to generate a dynamic pharmacophore model using the property mapping capability of the LigBuilder program. Compounds from the Available Chemicals Directory that fit the pharmacophore model were identified and have been submitted for experimental testing.The approach described here can be used as a valuable tool for the design of novel inhibitors of other biomolecular targets.     

Explanation of Theoretical Mechanism of Isomerization of L-Alanine Conformation for Experimental Results

B3LYP/6-31＋＋G＊＊ method was applied to investigate the mechanism of alanine isomerization.12 minima and 22 transition states were obtained after optimization and several paths of isomerization were found.It is found that intramolecular single-bond rotation and proton transfer might lead to isomerization.The energy barrier of C–N bond rotation was lower than 2.52 kcal·mol 1,while the energy barrier ranges of the rotation of C–C and C–O were separately 0.43~ 7.01 and 4.69~12.19 kcal·mol 1,and the minimum energy barrier of proton transfer was 30.76 kcal·mol 1.The most probable isomerization path and mechanism for the two most stable conformations was discussed to find that the highest energy barrier to be crossed in this path was 11.87 kcal·mol 1.In order to understand the microscopic nature why only 4 conformations were detected in the experiment,thermodynamic properties of all conformations at the experimental temperature of 391 K was calculated.It is found that conformations XII,XI,X and IX can only unidirectionally convert into conformations rapidly with low energy and vanish immediately.The other conformations were distributed according to Maxwell-Boltzman＇s law,and the distribution probabilities of conformations I,II,III,IV,V,VI,VII and VIII were respectively 27.2%,26.5%,25.8%,6.4%,5.2%,4.8%,2.5% and 1.6%.Conformations I,II and III with bigger probability and stronger absorption peak were easy to detect in the experiment.Conformation IV had a relatively smaller probability（6.4%） and weak absorption peak which,however,could also be identified.The other conformations had too small probability to identify in the spectrum.     

NaZnPO4催化碳酸二甲酯和丙氨酸“一锅法”合成N-羧基丙氨酸酸酐

以碳酸二甲酯（DMC）代替光气,一锅法合成α-氨基酸-N-羧酸酐（NCAs）是实现绿色制备多肽的重要途径.制备了酸碱协同催化剂NaZnPO₄,用该催化剂催化DMC和丙氨酸"一锅法"合成N-羧基丙氨酸酸酐（Ala-NCA）.在N,N-二甲基甲酰胺（DMF）溶剂中,150℃的反应条件反应8 h时,Ala-NCA的收率最高为46.84%,催化剂循环5次后收率仍达38.62%.NaZnPO₄中Zn²⁺和O-Na具有有效的酸碱协同催化作用,在反应过程中具有去质子化、精准酰基化和高效成环的作用.利用TG-MS-IR技术研究了催化剂表面上原料转化和中间体精准关环过程,并提出了可能的反应催化机理.     

Structures,g-tensors,and hyperfine coupling constants of L-α-alanine radicals in radiation dosimetry: An ab initio molecular dynamics simulation study

Alanine is used as a transfer standard dosimeter for gamma ray and electron beam calibration. An important factor affecting its dosimetric response is humidity which can lead to errors in absorbed dose calculations. Ab initio molecular dynamics calculations were performed to determine the environmental effects on the electron paramagnetic resonance (EPR) parameters of L-α-alanine radicals in acidic and alkaline solutions. A new result, not dissimilar to the closed-shell amino acid molecule alanine, is that the non-zwitterionic form of the alanine radical is the stable form in the gas phase while the zwitterionic neutral alanine radical is not a stable structure in the gas phase. Geometric and EPR parameters of radicals in both gas and solution phases are found to be dependent on hydrogen bonding of water molecules with the polar groups and on dynamic solvation. Calculations on the optimized free radicals in the gas phase revealed that for the neutral radical, hydrogen bonding to water molecules drives a decrease in the magnitudes of g-tensor components g _xx and g _yy without affecting neither g _zz component nor the hyperfine coupling constants (HFCCs). The transfer from the gas to solution phase of the alanine radical anion is accompanied with an increase in the spin density on the carboxylic group's oxygen atoms. However, for the neutral radical, this transfer from gas to solution phase is accompanied with the decrease in the spin density on oxygen atoms. Calculated isotropic HFCCs and g-tensor of all radicals are in good agreement with experiment in both acidic and alkaline solutions.