Uncatalyzed peptide bond formation between two double amino acid molecules in the gas phase

The gas phase mechanism for peptide bond formation between two double amino acid (DAA) molecules ((NH₂)₂C(COOH)₂) is investigated in the absence of any catalysts. Two different paths, concerted and stepwise, each leading to both cis and trans DAA‐DAA dipeptide products (four mechanisms total) are examined on the basis of theoretical calculations carried out at the CCSD(T)/aug‐cc‐pVDZ//MP2/aug‐cc‐pVDZ level. The investigation indicates that the concerted mechanism leading to the trans configuration of the peptide bond in the DAA‐DAA dipeptide product is thermodynamically favored by about 5 kcal mol^?1 and requires slightly less energy than the remaining pathways considered. Moreover, the peptide bond formation process between two DAA molecules in the gas phase resembles the analogous reactions between two natural amino acids.     

微波无溶剂法合成香草醛氨基酸席夫碱

氨基酸席夫碱是制备特殊生物活性物质的重要中间体。氨基酸席夫碱中的亚胺(C=N)结构与亚磷酸烷基酯加成的化合物具有良好的抗植物病毒,除草,杀菌等性能[1-3]。氨基酸席夫碱中的羟基,羧基和亚胺等多个活性基团,可以与多种金属离子配位,其配合物具有抗菌,抗病毒,抗癌等性能[4-9],     

Direct peptide coupling of novel amino acid derivatives produced by rearrangement of catalytically generated ammonium ylides

Protected amino acids can be prepared from substrates in which a diazo ester is aryl-tethered to an allylic amine, by catalytic intramolecular ammonium ylide generation and [2,3] rearrangement. When the aryl tether is sufficiently electron-deficient, direct coupling of the rearrangement product with a hindered amino acid ester to give a dipeptide is possible, and ammonium ylide generation, rearrangement and peptide coupling can be accomplished in a one-pot fashion.     

Toward the origin of life over feldspar surfaces: Adsorption of amino acids and catalysis of conformational interconversions

Feldspars are a group of tectosilicate minerals terminated with a full layer of hydroxyl groups and have been regarded as “hotbed” for birth of life. In this study, periodic density functional theory calculations are conducted to address two associated issues, as adsorption of amino acids and conformational interconversions over feldspar surfaces. Distribution of glycine isomers depends strongly on the number of interacted surface silanols (n), and canonical isomers exist exclusively for n ≤ 2 while zwitterions predominate for n = 3. Adsorption of amino acids is significantly affected by sidechains, especially those forming H-bonds with surfaces; however, sidechain contacts with feldspar surfaces disfavor zwitterion stabilization, and zwitterions become preferred without sidechain contacts. For all amino acids, conformational interconversions undergo four elementary steps, and proton transfer between two carboxylic-O atoms (step 2) is always rate-decisive. Step 2 is greatly accelerated with catalysis of surface silanols and activation barriers depend significantly on sidechains. All amino acids have moderate activation barriers and conformational interconversions (in both forward and reverse directions) proceed favorably at ambient conditions. Sidechains of amino acids exhibit influences through sidechain contacts with surfaces rather than as substituent effect.     

Phosphoryl group differentiating α‐amino acids from β‐ and γ‐amino acids in prebiotic peptide formation

In recent years β‐amino acids have increased their importance enormously in defining secondary structures of β‐peptides. Interest in β‐amino acids raises the question: Why and how did nature choose α‐amino acids for the central role in life? In this article we present experimental results of MS and ³¹P NMR methods on the chemical behavior of N‐phosphorylated α‐alanine, β‐alanine, and γ‐amino butyric acid in different solvents. N‐Phosphoryl α‐alanine can self‐assemble to N‐phosphopeptides either in water or in organic solvents, while no assembly was observed for β‐ or γ‐amino acids. An intramolecular carboxylic–phosphoric mixed anhydride (IMCPA) is the key structure responsible for their chemical behaviors. Relative energies and solvent effects of three isomers of IMCPA derived from α‐alanine (2a–c), with five‐membered ring, and five isomers of IMCPA derived from β‐alanine (4a–e), with six‐membered ring, were calculated with density functional theory at the B3LYP/6‐31G** level. The lower relative energy (3.2 kcal/mol in water) of 2b and lower energy barrier for its formation (16.7 kcal/mol in water) are responsible for the peptide formation from N‐phosphoryl α‐alanine. Both experimental and theoretical studies indicate that the structural difference among α‐, β‐, and γ‐amino acids can be recognized by formation of IMCPA after N‐phosphorylation. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem 94: 232–241, 2003     

铈氨基酸配合物对Oliogo DNA 的切断

小分子与生物大分子的作用是近年来一个活跃的研究领域,其中稀土金属离子及其配合物与DNA的相互作用的研究逐渐受到关注。能够以水解方式切割DNA的体系还非常少,不多的几个例子都集中在Ce4+上[1～4]。本文采用循环伏安法,紫外光谱法,变性聚丙烯酰胺凝胶电泳 银染法,研究了几种铈氨基酸配合物以及这几种配合物与单链寡聚脱氧核苷酸(OligoDNA)的水解切断作用。1　实验部分1.1　仪器和试剂CHI600A电化学分析仪(上海辰华仪器公司),HP8451A紫外分光光度计(美国HP公司),垂直式电泳槽(上海华永工贸有限公司),稳压稳流电泳仪(DYY Ⅲ2,…     

微波辐射在合成沙利度胺的铵盐类衍生物中的应用

沙利度胺(Thalidomide)又名反应停,化学名称为N-2-(2,6-二氧-3-哌啶基)-邻苯二甲酰亚胺[N-2-(2,6-dioxo-3-piperidinyl)-phthalidomide],是一种合成类谷氨酸衍生物,曾因致畸副作用而一度停止对其的研究[1].但上个世纪末期,Sampaio[2]等曾报道,沙利度胺可抑制体外LPS刺激原代人体单核细胞生成TNF-α,Kenyon[3]等的研究表明(S)-沙利度胺有着很强的抑制血管生成作用,再度引发了科学界对沙利度胺及其相关衍生物的研究兴趣.     

Microwave-assisted digestion procedures for biological samples with diluted nitric acid: Identification of reaction products

Microwave-assisted sample preparation using diluted nitric acid solutions is an alternative procedure for digesting organic samples. The efficiency of this procedure depends on the chemical properties of the samples and in this work it was evaluated by the determination of crude protein amount, fat and original carbon. Soybeans grains, bovine blood, bovine muscle and bovine viscera were digested in a cavity-microwave oven using oxidant mixtures in different acid concentrations. The digestion efficiency was evaluated based on the determination of residual carbon content and element recoveries using inductively coupled plasma optical emission spectrometry (ICP OES). In order to determine the main residual organic compounds, the digests were characterized by nuclear magnetic resonance (¹H NMR). Subsequently, studies concerning separation of nitrobenzoic acid isomers were performed by ion pair reversed phase liquid chromatography using a C18 stationary phase, water:acetonitrile:methanol (75:20:5, v/v/v) + 0.05% (v/v) TFA as mobile phase and ultraviolet detection at 254 nm. Sample preparation based on diluted acids proved to be feasible and a recommendable alternative for organic sample digestion, reducing both the reagent volumes and the variability of the residues as a result of the process of decomposition. It was shown that biological matrices containing amino acids, proteins and lipids in their composition produced nitrobenzoic acid isomers and other organic compounds after cleavage of chemical bonds.     

焦磷酸盐-磷酸盐复合催化剂高效催化乳酸脱水制丙烯酸

利用沉淀法制得焦磷酸盐与磷酸盐在浆状态下复配制备成复合催化剂,并用于催化乳酸脱水制丙烯酸.实验发现催化剂的组成对乳酸的转化率及丙烯酸的选择性有着重要的影响,当磷酸盐/焦磷酸盐质量比在30∶70～50∶50范围内,可以获得较高的乳酸的转化率和丙烯酸的选择性.催化反应条件如反应温度,乳酸进料浓度,液空速也被详细地进行了考察.此外,考察了该复合催化剂的稳定性.当催化剂连续运行56 h后,乳酸的转化率保持在96%以上,丙烯酸的选择性也高达57%.为了进一步揭示催化剂的结构与催化性能之间的关系,利用X射线粉末衍射、热重、扫描电镜和傅立叶红外等对催化剂进行了表征.     

Locating apoptosis proteins by incorporating the signal peptide cleavage sites into the general form of Chou's Pseudo amino acid composition

Apoptosis proteins play an essential role in the development and homeostasis of an organism. The accurate prediction of subcellular location for apoptosis proteins is helpful for understanding the mechanism of programmed cell death and their biological functions. In this article, a new apoptosis proteins localization algorithm, named PSSP, is proposed based on the predicted cleavage sites of primary protein sequences. First, protein chains are divided into N‐terminal signal parts and mature protein parts according to their predicted cleavage sites by SignalP. Then, amino acid composition (ACC) of the individual subsequence together with pseudo‐ACC and stereochemical properties of whole chain were extracted to represent a given protein sequence. Jackknife test by support vector machine on three broadly used datasets (ZD98, ZW225, and CL317 datasets) of apoptosis proteins demonstrated that the total accuracies by this approach are 93.9, 87.6, and 91.5%, respectively. In addition, an independent nonapoptosis benchmark dataset (NNPSL) was also used to evaluate the performance of this method, and predictive accuracies for eukaryotic and prokaryotic proteins are also comparable to existing methods. © 2013 Wiley Periodicals, Inc.     

N-3 alkylation of uracils with unprotected amino alcohols using the Mitsunobu reaction

During our search for novel CGRP antagonists, we had great difficulty in accessing one of our key motifs. Herein, we communicate how we solved the problem by an unprecedented Mitsunobu alkylation using unprotected amino alcohols.     

氨基膦酸树脂吸附镨的研究

氨基膦酸树脂 (简称ＡＰＡＲ)是一类性能优良的螯合树脂 ,功能基为 ＣＨ2 ＮＨＣＨ2 Ｐ(Ｏ) (ＯＨ) 2 ,由于功能基上同时含有Ｎ和Ｏ等配位原子 ,它能与多种金属离子形成比较稳定的配合物。近年来有关含磷的螯合树脂吸附金属离子的各种研究比较活跃[1～ 4] 。本文就氨基膦酸树脂在ＨＡｃ ＮａＡｃ体系中对镨 (Ⅲ )的吸附行为进行了研究。获得了诸多基本参数 ,为氨基膦酸树脂在湿法冶金中对镨离子的富集、提取等方面的应用提供了理论依据。1　实验部分1 1　试剂及仪器72 1型分光光度计 ,ＳＨＡ Ｃ水浴恒温振荡器(± 0 .1℃ ) ,ｐＨＳ 3ｃ型…     

Thermodynamic quantities for the protonation of amino acid amino groups from 323.15 to 398.15 K

Flow claorimetry has been used to study the interaction of protons with glycine, DL--alanine, -alanine, DL-2-aminobutyric acid, 4-aminobutyric acid, and 6-aminocaproic acid in aqueous solutions at temperatures from 323.15 to 398.15 K. By combining the measured heats for amino acid solutions titrated with NaOH solutions with the heat of ionization for water, the log K, H^o, S^o, and C_p ^o values for the protonation of the amino groups of these amino acids have been obtained at each temperature studied. Equations are given expressing these values as functions of temperature. The H^o and S^o values increase while log K values decrease as temperacture increases. The trends for log K, H^o, S^o, and C_p ^o are discussed in terms of changes in long-range and short-range solvent effects. The trend in H^o, S^o, and C_p ^o values with temperature and with charge separation in the zwitterions is interpreted in terms of solvent-solute interactions and the electrostatic interaction between the two oppositely charged groups within the molecule.     

N-磷酰化氨基酸生成五配位磷中间体过程中氨基酸侧链立体化学效应的理论研究

用密度泛函(DFT)方法在B3LYP/6-311G(d,p)水平上对N-磷酰化氨基酸生成五配位磷酸羧酸混酐(IMCPA)反应中手性氨基酸残基侧链的立体化学效应进行了研究. 模拟了氨基酸残基上羧基氧原子从磷酰基的不同侧面进攻磷原子从而形成不同构型五配位磷中间体的反应途径, 探讨了IMCPA生成过程中的立体选择性.     

基于电子舌技术的氨基酸与密码子关系的初步研究

自从首个遗传密码子被破译以来,密码子与所表达的氨基酸之间的关系一直吸引了许多关注.本研究从氨基酸、核苷和三偏磷酸钠的反应体系出发,用电子舌检测反应前后体系变化,考察核苷对氨基酸成肽反应的影响,试图找到氨基酸与密码子的联系.结果表明,大部分氨基酸的密码子或反密码子中间位核苷对反应的促进作用最大,这种结果可能是因为核苷的碱基与氨基酸的侧链基团之间的某种弱相互作用导致的.相应地,亮氨酸和异亮氨酸之间的结果差异更加佐证了上述假设.这种弱相互作用有望成为研究密码子识别氨基酸的关键突破,为生命起源的研究提供新方法.     

ICTC-RAAC: An improved web predictor for identifying the types of ion channel-targeted conotoxins by using reduced amino acid cluster descriptors

Conotoxins are small peptide toxins which are rich in disulfide and have the unique diversity of sequences. It is significant to correctly identify the types of ion channel-targeted conotoxins because that they are considered as the optimal pharmacological candidate medicine in drug design owing to their ability specifically binding to ion channels and interfering with neural transmission. Comparing with other feature extracting methods, the reduced amino acid cluster (RAAC) better resolved in simplifying protein complexity and identifying functional conserved regions. Thus, in our study, 673 RAACs generated from 74 types of reduced amino acid alphabet were comprehensively assessed to establish a state-of-the-art predictor for predicting ion channel-targeted conotoxins. The results showed Type 20, Cluster 9 (T = 20, C = 9) in the tripeptide composition (N = 3) achieved the best accuracy, 89.3%, which was based on the algorithm of amino acids reduction of variance maximization. Further, the ANOVA with incremental feature selection (IFS) was used for feature selection to improve prediction performance. Finally, the cross-validation results showed that the best overall accuracy we calculated was 96.4% and 1.8% higher than the best accuracy of previous studies. Based on the predictor we proposed, a user-friendly webserver was established and can be friendly accessed at http://bioinfor.imu.edu.cn/ictcraac.     

Use of N-trifluoroacetyl-protected amino acid chlorides in peptide coupling reactions with virtually complete preservation of stereochemistry

The use of protected amino acid chlorides for peptide coupling reactions has long been avoided due to the extensive racemization that commonly occurs during either the acid chloride formation or the coupling reaction itself. Conditions are described which allow N-trifluoroacetyl-protected amino acid chlorides to be generated in high purity and with high retention of stereochemical integrity. Control of temperature is the predominant factor in controlling racemization, and rapid formation of acid chlorides under low temperature can be conveniently achieved using Vilsmeier reagent. Stereochemical integrity is further maintained when coupling of N-trifluoroacetyl acid chlorides is carried out with amino acid esters under Schotten-Baumann conditions using specific controls on pH, temperature, and agitation. Second order rate constants for coupling and the azlactone formation associated with racemization were measured to be 4260 and 3.6 L/mol s, respectively. This high rate differential allows for the reaction to be run with a minimum excess of amine ester, and makes it suitable for continuous processing. The applicability of the preferred coupling conditions to a range of amino acid couplings is described.