Chiral Recognition of Dansyl Derivatives with an Amino Acid-Based Molecular Micelle: A Molecular Dynamics Investigation

In this study, the chiral separation mechanisms of Dansyl amino acids, including Dansyl-Leucine (Dans-Leu), Dansyl-Norleucine (Dans-Nor), Dansyl-Tryptophan (Dans-Trp) and Dansyl-Phenylalanine (Dans-Phe) binding to poly-sodium N-undecanoyl-(L)-Leucylvalinate, poly (SULV), were investigated using molecular dynamics simulations. Micellar electrokinetic chromatography (MEKC) has previously shown that when separating the enantiomers of these aforementioned Dansyl amino acids, the L-enantiomers bind stronger to poly (SULV) than the D-enantiomers. This study aims to investigate the molecular interactions that govern chiral recognition in these systems using computational methods. This study reveals that the computationally-calculated binding free energy values for Dansyl enantiomers binding to poly (SULV) are in agreement with the enantiomeric order produced in experimental MEKC studies. The L-enantiomers of Dans-Leu, Dans-Nor, Dans-Trp, and Dans-Phe binding to their preferred binding pockets in poly (SULV) yielded binding free energy values of -21.8938, -22.1763, -21.3329 and -13.3349 kJ·mol-1, respectively. The D-enantiomers of Dans-Leu, Dans-Nor, Dans-Trp, and Dans-Phe binding to their preferred binding pockets in poly (SULV) yielded binding free energy values of -14.5811, -15.9457, -13.6408, and -12.0959 kJ·mol-1, respectively. Furthermore, hydrogen bonding analyses were used to investigate and elucidate the molecular interactions that govern chiral recognition in these molecular systems.

Synthesis of a pair of novel receptors and their properties of enantioselective recognition for amino acid zwitterions

A pair of artificial enantiotopic receptors la and lb composed of (S,S) or (R,R) chiral bicyclic guanidinium, azacrown ether and (t-butyldiphenylsilyloxy) methyl group for amino acid zwitterions have been synthesized. The liquid-liquid competition experiments and 1 H NMR studies indicate that the receptor 1a with (S, S) configuration and 1b with (R,R) configuration selectively recognize L- and D-aromatic amino acids & respectively.

Design and synthesis of chiral single-armed molecular tweezers derived fromα-hyodeoxycholic acid

A novel type of molecular tweezers with different chiral center and cleft has been designed and prepared by using α- hyodeoxycholic acid as spacer and D/L-amino acid methyl ester as chiral arm attached at 3-position. Their structures were elucidated by ^1H NMR, FTIR and elemental analysis. Their recognition properties for various D/L-amino acid methyl esters were also investigated. The preliminary results indicated that these chiral single-armed molecular tweezers exhibited good recognition ability for D/L-amino acid methyl esters with high association constant （up to 5.24 × 10^3 L mol^-1）.

Design and synthesis of novel chiral molecular tweezers based on deoxycholic acid

A novel type of chiral molecular tweezers has been designed and synthesized by using deoxycholic acid as backbone and ethanoyl and the chiral unsymmetrical urea unit as arms. Their structures were characterized by 1H NMR, IR, MS spectra and elemental analysis. These molecular tweezers showed good binding ability for neutral molecules and chiral molecules.

Design and Synthesis of Chiral Molecular Tweezers Based on Deoxycholic Acid

A series of new chiral molecular tweezers have been designed and synthesized by using deoxycholic acid as spacer and aromatic amines as arms. Instead of using toxic phosgene, the triphosgene was employed in synthesis of the molecular tweezers receptors. These chiral molecular tweezers showed good enantioselectivity for D-amino acid methyl esters.

New Chiral Calixarene Derivatives: Syntheses and Their Chiral Recognition Toward Amino Acids by UV-Vis Spectroscopy

Three novel types of chiral calixarene derivatives 5, 8, and 10 were designed and synthesized by introducing chiral units to parent calixarenes. Their chiralities were confirmed by rotational analysis. Chiral recognition properties of these host compounds towards L- and D-threonine were studied by UV-Vis spectroscopy. The results indicated that calixarene derivatives 5 and 8 exhibited good chiral recognition capabilities toward L- or D-threonine. Although calixarene derivative 10 had no evident chiral recognition ability, the supramolecules of calixarene derivative 10 with L- or D-threonine showed a hypochromic effect or hyperchromic effect respectively. Therefore, calixarene derivative 10 might serve as a good chiral UV-indicator.

Design and Synthesis of Novel Molecular Tweezers Derived from Chenodeoxycholic Acid

A novel type of chiral molecular tweezers has been designed and synthesized by using chenodeoxy cholic acid as spacer and the aromatic compounds as arm. Their structures were characterized by 1HNMR, IR, MS spectra and elemental analysis. These chiral molecular tweezers showed good enantioselectivity for D-amino acid methyl esters.

Binol Based Chirality Conversion Reagents for Underivatized Amino Acids

Four binol based pyrrole carboxamide chiral receptors has been synthesized and effectively used as a Chirality Conversion Reagent (CCR) for underivatized amino acids. Three points of interactions take place for the conversion process. They are the reversible imine formation, the internal resonance assisted Hydrogen Bonding (RAHB) and the additional hydrogen bonds between the amino acids and the heterocylic moiety of the pendant groups. The conversion efficiency of all the receptors was found to be comparable with those of the receptors reported earlier.

Molecular recognition on supramolecular systems (XXXV)——Synthesis of novel β-cyclodextrin derivative bearing pyridinio group and its chiral discrimination of amino acids

A novel p-cyclodextrin derivative 4 bearing a pyridinio group on the primary side was synthesized by the reaction of 2-aminopyridine with 6-p-cyclodextrin monoaldehyde 3, and its complexation stability constants with several aliphatic amino acids have been determined in phosphate buffer solution ( pH = 7.2, 0.1 mol ?L^(-1)) at 25℃by using spectrofluorometric titrations. The stoichiometry is 1 : 1 for the inclusion complexation of amino acids with compound 4. Circular dichroism study indicates that the aromatic moiety was embedded shallowly into the cyclodextrin cavity. As a spectral probe, the pyridinio group in the modified cyclodextrin can recognize not only differences of the size and shape of amino acid molecules, but also the L/D-amino acid chiral iso-mer. As compared with mono-[6-(1-pyridinio)-6-deoxy]-p-cyclodextrin 5, compound 4 switched the enantiomer preference for L- to D-isomer, and showed the highest enantioselectivity of 5.4 for D/L-serine. These results are discussed from the viewpoints of geometric compensation, induced-fit concept and cooperation of several weak interactions.

Molecular recognition study on supramolecular system (Ⅶ)-——Chiral recognition of amino acids with α-cyclodextrin using competitive inclusion method

CYCLODEXTRINS (CDs) have been extensively studied. The studies mainly focused on their in-clusion complexation with guest molecules for mimicking the enzyme-substrate specific interac-tion. The molecular recognition mainly involves several classes of organic compounds, such ashydrocarbon, aliphatic alcohols, aliphatic diols, phenols, cyclohexane derivatives, naphtha-lene derivatives, and other aromatic compounds, but few amino acid molecules.

Molecular recognition study on supramolecular system (Ⅲ)——Chiral recognition of aromatic amino acids by binuclear Cu(Ⅱ) complexes with cyclodextrins

The study of supramolecular species formed by the selective binding of substrate(guest) with a molecular receptor (host) is currently a signficant topic in chemistry,biochemistry, and so on. Natural and chemically modified cyclodextrins (CDs) having fairlyrigid and well-defined hydrophobic cavities can be taken as a molecular receptor to recog-nize a wide variety of organic, inorganic, and biological guest molecules, forming host-guestcomplexes or supramolecutar species, which have been applied to several areas of scienceand technology as an excellent model system mimicking the substrate-specific interaction

An Efficient Synthesis of Selective Human NR2A Antagonist NVP-AAM077

A short and efficient synthesis of the selective human N-methyl-D-aspartate （NMDA） receptor 2A （NR2A） antagonist NVP-AAM077 is described. The target was achieved in 8 steps and in 54% overall yield from the commercially available chemical 3-methylbenzene-1,2-diamine. A NaIO4/DMF-based oxidation of the bromide to corresponding aldehyde and an addition of phosphinic acid ester to the aldimine successfully served as the key steps.

水溶性荧光探针在氨基酸分子识别中的研究进展

氨基酸作为一类重要的生物小分子,既是构成蛋白质的基本单元,同时也参与多种生理过程,包括神经系统调节、免疫功能调节及能量供应等。此外,光学纯的氨基酸还可以作为不对称合成与催化的手性源和手性配体。因此,氨基酸的化学选择性和对映选择性识别在生命医药和不对称合成领域均有深远的研究意义。基于荧光探针高灵敏性、实时性和易于操作的优势,以及分析底物氨基酸的优良水溶性,开发水相中对氨基酸具有优异分子识别能力的荧光探针是一项重要的工作。综述了近五年应用于氨基酸分子识别的水溶性荧光探针研究进展,并展望了该领域的研究方向。

关于5-HT 2A受体关键氨基酸位点的研究进展

5-HT 2A受体作为许多精神活性药物如致幻剂、抗抑郁药、抗焦虑药和非典型抗精神病药等的作用靶点,一直是神经精神药理学领域研究热点。5-HT 2A受体的某些关键氨基酸位点对于维持受体的特定构象、偶联不同G蛋白以及行使相应特定功能等起重要作用。进一步的研究显示,突变这些特定的氨基酸位点,能够引起相应配体的亲和力、效能等变化。同时,5-HT 2A受体作为一种典型的G蛋白偶联受体,其结构域中不同的氨基酸位点能与不同配体产生相互作用,引起受体相应的动态结构变化,从而影响受体的功能。因此,研究5-HT 2A受体结构和功能与关键氨基酸位点的关系,对于相关精神疾病的治疗以及设计高效低毒的新型药物具有重要意义。

Synthesis and anti-tumor activities of novel 7-O-amino acids chrysinderivatives

Objective: To design and synthesize a series of chrysin derivatives and evaluate the antitumor activities with MTT assay, so as to investigate molecular structure-activity relationship with molecular docking.Methods: Target products were synthesized with high yield by substitution reaction, hydrolysis reaction,esterification reaction, and saponification reaction in sequence, and activities of all compounds were evaluated with human gastric carcinoma cell lines MGC-803 and human breast carcinoma cell lines MCF-7 through standard MTT assay. Molecular docking results were calculated with Surflex Geom X programme of Sybyl X-2.0 version workstation.Results: 7-O-amino acids chrysin derivatives 6 a–6 l were synthesized and their inhibitory effects were evaluated by comparing the material chrysin with positive control drug 5-fluorouracil(5-FU). Among these derivatives, compound 5 b(IC50= 24.50 ± 2.26 μmol/L), 5 k(IC50= 24.30 ± 2.19 μmol/L), and 6 f(IC50= 24.61 ± 2.01 μmol/L) showed better inhibitory activities against MGC-803 cell lines, and compound 5 g(IC50= 13.15 ± 1.73 μmol/L) and 5 j(IC50= 12.34 ± 1.25 μmol/L) showed better inhibitory activities against MCF-7 cell lines than chrysin and 5-FU. Molecular docking scores showed a credible consistency compared with MTT results.Conclusion: Compounds 5 b, 5 d, 5 g, 5 j, 5 k, and 6 f showed good antiproliferative effects on specific tumor cells, and compound 5 g should be researched further when according to molecular docking.

手性氨基酸尾式卟啉锌配合物对氨基酸酯的手性分子识别

手性氨基酸尾式卟啉锌配合物对氨基酸酯的手性分子识别罗国添刘海洋黄锦汪彭小彬计亮年（中山大学化学系，广州５１０２７５）关键词氨基酸尾式卟啉锌配合物，氨基酸酯，手性识别分类号Ｏ６１４．２４１在蛋白质的生物合成中，氨酰ｔ－ＲＮＡ合成酶对氨基酸表现出极为专...

胆甾类分子钳对氨基酸衍生物的对映选择性识别

用差紫外光谱滴定法考察了以脱氧胆酸作spaer的手性分子钳1～3对一系列α-氨基酸甲酯的对映选择性识别性能.结果表明,分子钳1和2与客体氨基酸甲酯形成1:1型超分子配合物,并显示较好的手性识别能力.分子钳3对所考察的氨基酸甲酯均没有明显的识别作用.讨论了主-客体间尺寸/形状匹配、几何互补等因素对形成超分子配合物的影响,并利用计算机模拟作辅助手段对实验结果和现象进行了解释.

氨基甲酸酯型脱氧胆酸分子钳对氨基酸甲酯的手性识别研究

以脱氧胆酸为spacer,通过三光气桥连各种芳胺 ,合成了新的氨基甲酸酯型分子钳受体 1～ 4.这些化合物的结构经IR ,1HNMR和元素分析所证实 .利用差光谱滴定法考察了其与D/L氨基酸甲酯的对映选择性识别性能 .结果表明 ,分子钳 1～ 4对所考察的氨基酸甲酯均具有识别能力 ,其对D 氨基酸甲酯的识别优于对L 氨基酸甲酯的识别 .从主客体间的大小形状匹配及几何互补关系等方面对这些受体的识别能力及对映选择性进行了讨论 .

新型手性咪唑鎓环番的合成及对氨基酸的对映选择性识别

以L-氨基酸为手性源，合成了一系列新型手性咪唑鎓环番，并进行了结构表征．在碱性条件下，L-氨基酸和乙二醛、甲醛缩合生成了（S）-2-（1-咪唑）羧酸钠，转化为甲酯后与乙二胺进行胺解反应制得开链手性咪唑二酰胺，然后与二溴化合物在高稀淡技术和无水条件下进行季铵化关环反应，再进行阴离子交换制得目标分子（4—6）．以手性咪唑鎓环番为主体分子，研究了对氨基酸及其衍生物的对映选择性识别作用．

水溶性手性Salen Mn(III)的光谱性质及其对氨基酸客体的分子识别研究

合成并表征了手性配体SalenH2 及其锰配合物 .详细讨论了配体及配合物的红外光谱、电子吸收光谱和圆二色光谱性质 .研究结果表明 ,SalenMn(III)配合物在水溶液中为Δ构型 ,进一步证明了配合物中双偶氮螯环结构的确具有很高的刚性 .用紫外 -可见光谱滴定方法测定了锰配合物与氨基酸分子识别过程的缔合常数 ,实验结果表明 :主体SalenMn(III)对每一对氨基酸对映异构体的识别能力均表现为对D 型的识别能力比对L 型大 ,对具有相同对映构型的不同氨基酸客体的识别能力按Phe ,Val和Thr顺序依次递减 .圆二色光谱 (CD)考察结果与热力学研究结果一致 .此外 ,采用分子力学方法考察了主客体体系的最低能量构象 ,并对该构象进行了量子化学计算 ,从理论上对实验事实作了进一步解释 .