谷胱甘肽过氧化物酶模拟物碲化透明质酸的合成及催化动力学研究

 以透明质酸(HA)作为谷胱甘肽过氧化物酶(GPX)的酶模型,将碲(Te)引入HA中,合成了一种新型的高活力的GPX模拟物碲化透明质酸(TeHA). 用红外光谱和核磁共振技术对TeHA的结构进行了研究,证明Te的修饰位点位于HA的N-乙酰氨基葡萄糖的羟甲基(-CH2OH)上. 采用Wilson辅酶偶联法测定得到TeHA催化还原型谷胱甘肽(GSH)还原H2O2的GPX活力为163.6 U/μmol, 高于文献报道的其它模拟酶. TeHA还能够催化GSH还原异丙苯基过氧化物(CuOOH)和叔丁基过氧化物(t-BuOOH)的反应,并且CuOOH为该模拟酶的最适底物. 通过研究TeHA催化GSH还原三种不同过氧化物的反应动力学发现, TeHA的催化遵循乒乓机制.     

基于透明质酸构建的功能材料及其在生物医药领域中的应用

透明质酸(HA)是由D-葡萄糖醛酸和N-乙酰基葡萄糖胺二糖重复单元组成的线性聚阴离子多糖.目前,HA的研究和应用主要体现在3个方面:(1)基于HA分子含有的羟基、羧基和乙酰氨基等官能团,制备各类衍生物和水凝胶;(2)基于HA分子能与癌细胞表面的受体(如分化簇44(CD44)、淋巴管内皮细胞受体1(LYVE-l)、HA内...     

透明质酸及其衍生物作药物载体

透明质酸(HA)具有良好的生物相容性和生物降解性，是优良的药物载体。但其稳定性差，对强酸、强碱、热、自由基及透明质酸酶敏感，容易发生降解而限制了其应用。本文简要介绍HA的基本特性及应用，重点阐述了HA经不同的化学改性方法如酯化、交联、接枝所得衍生物作药物载体的最新研究进展。化学改性赋予了HA一系列的优良特性,如适当的机械强度、特殊的流变学特性、良好的稳定性、靶向性等,可提高、扩大HA作药物载体的性能和应用范围。最后展望了透明质酸及其衍生物作药物载体的应用前景。     

藏红T作为电化学探针线扫极谱法测定透明质酸

在pH 1.5的B ritton-Rob inson(B-R)缓冲溶液中,藏红T(ST)在-0.35 V(vs.SCE)处有一个灵敏的线性扫描二阶导数极谱还原波。当加入一定量的透明质酸(HA)后,由于此条件下ST带正电荷,而HA带负电荷,两者之间通过静电力作用形成一种生物超分子复合物,导致溶液中游离的ST的浓度降低,相应的还原峰电流降低。实验优化了结合反应条件和电化学测定条件。在最佳条件下,还原峰电流的降低值与HA的浓度在3.0~100.0 mg/L范围内呈线性关系,线性回归方程为Δip(″nA/s-2)=27.23 15.18C(mg/L)(n=14,r=0.996),本方法成功应用于HA模拟样品的测定。     

生物素功能化透明质酸二糖的合成

透明质酸(Hyaluronic Acid, HA)是细胞外基质的组成部分，它与细胞表面受体CD44的相互作用在许多生物事件如细胞的增殖与转移等中发挥着重要作用，由于CD44-HA的结合对于下游信号传导至关重要，能选择性地破坏HA-CD44复合物形成的化合物可以用作CD44介导的细胞事件的有用探针以及用于治疗这些事件引起的疾病的潜在新方法。为此本文报道一个有可能干预HA-CD44复合物形成的化合物生物素功能化的透明质酸二糖(HA2)类似物的合成，以全保护的氨基葡萄糖2为起始物，经过13步反应，以15%的最终收率得到生物素功能化的HA2。目标产物和关键中间体都经过核磁共振氢谱、碳谱，ESI-质谱或高分辨质谱表征。     

基于透明质酸的刺激响应纳米给药系统的研究进展

透明质酸(Hyaluronic acid, HA)是一种天然多糖,具有良好的生物相容性和生物降解性,利用 HA 构建的纳米载体自身就具有肿瘤靶向功能,可以作为抗癌药物载体将药物传递到肿瘤细胞内从而实现精准到达病患处。近年来透明质酸在应用于肿瘤靶向给药系统中的关注越来越多,成为了靶向治疗肿瘤的一大研究热点。基于透明质酸的基本特性和肿瘤靶向的生理学基础,在不同的刺激响应下,透明质酸型纳米给药系统能将药物集中释放于肿瘤的微环境内,更好地杀死肿瘤细胞,同时避免其他正常的组织受到药物损害。本文主要综述了透明质酸型纳米药物输送系统在各种刺激响应下释放药物的最新研究进展。     

以透明质酸为骨架的新型谷胱甘肽过氧化物酶(GPX)模拟酶的制备及性质研究

用修饰法合成以透明质酸为骨架的两种新型GPX模拟酶: 硒化透明质酸SeHA及碲化透明质酸TeHA. 用红外光谱和核磁共振波谱对模拟酶的结构进行研究, 证明其修饰位点位于透明质酸的N-乙酰氨基葡萄糖的—CH2OH. 用二硫代双硝基苯甲酸(DTNB)法测定模拟酶的硒含量为1.2%. 通过模拟酶对3种不同底物过氧化氢(H2O2)、过氧化氢正丁烷(t-BuOOH)和过氧化氢异丙苯(CuOOH)的催化活性的研究结果表明CuOOH为该反应的最佳底物. 研究模拟酶催化谷胱甘肽(GSH)还原3种过氧化物的动力学发现, 反应速率与底物浓度的双倒数曲线均为平行的直线, 说明模拟酶反应的动力学机制与天然GPX相同, 为乒乓机制. 用2,4-二叔丁基甲基苯酚(BHT)法证明了该催化反应为非自由基机理, 且模拟酶不易被碘乙酸抑制.     

透明质酸-量子点的制备及应用

基于量子点(QD)独特的光学成像特性, 采用化学合成法制备了透明质酸(HA)修饰的水溶性纳米量子点(HA-QD), 并将其应用于特异性受体CD44的识别研究中. 体外细胞实验结果证实, 在透明质酸受体的介导下, 该纳米复合物可使小鼠肺腺癌细胞LA795显示特异性的荧光成像. 本研究为建立针对透明质酸受体的肿瘤活体检测及研究肿瘤的发生发展提供了重要的纳米靶向荧光探针.     

一种新型CO_2响应型肿瘤靶向药物传递载体

将透明质酸(HA)依次接枝1,12-二氨基十二烷和N,N-二甲基乙酰胺二甲缩醛(DADA),构建得到CO_2刺激响应的透明质酸-脒基(HA-ami)。为了考察其结构、CO_2刺激响应性、细胞水平作为药物载体的可行性和肿瘤靶向性,进行了结构表征、CO_2刺激响应性表征、细胞摄取、细胞毒性和体内的组织分布实验。结果表明:HA-ami成功构建,并具有一定的CO_2刺激响应性,可携带模型药物摄取进入人乳腺癌细胞(MCF-7),而且没有出现明显的细胞毒性,具有体内肿瘤靶向性。     

温敏性异丙基丙烯酰胺-二氧化硅透明质酸核壳型杂化微凝胶的合成和体积相变行为

通过溶胶-凝胶法,利用硅烷偶联剂(KH550)对纳米SiO2颗粒进行原位改性,使其表面带正电。改性后的SiO2颗粒(MSiO2)通过静电作用吸附带负电的透明质酸(HA)形成核壳颗粒(HA-MSiO2)。进一步在壳层HA链上接枝聚合N-异丙基丙烯酰胺(NIPAM)制得核壳结构温敏性杂化微凝胶(PNIPAM-HA-MSiO2),并用AFM和SEM表征其在云母表面的成膜性能。结果表明:HA-MSiO2核壳颗粒平均粒径约为182 nm,壳层厚度15 nm,其粒径或壳层厚度可以通过改变MSiO2溶液或HA溶液的浓度来调节;温敏性PNIPAM-HA-MSiO2微凝胶的体积相变温度为32°C,与PNIPAM溶液的最低临界溶解温度(LCST)一致,在体积相变温度以下旋涂于云母表面的微凝胶呈现球形颗粒,体积相变温度以上旋涂膜可以转变为致密的膜。     

Synthesis of two hyaluronan trisaccharides

[formula: see text] The synthesis of two hyaluronan trisaccharides, methyl O-(beta-D-glucopyranosyluronic acid)-(1,3)-O-(2-acetamido-2-deoxy-beta-D-glucopyranosyl)-(1,4)-O-beta-D- glucopyranosiduronic acid and methyl O-(2-acetamido-2-deoxy-beta-D-glucopyranosyl)-(1,4)-O-beta- D-glycopyranosyluronic acid)-(1,3)-O-(2-acetamido-2-deoxy-beta-D-glucopyranoside, are described. Construction of the target molecules was achieved though a combination of the phenyl sulfoxide and trichloroacetimidate glycosylation methodologies. This is the first report on the synthesis of the beta-methyl derivatives, which represent the smallest fragments that incorporate all the structural features of polymeric hyaluronan.     

Globo H四糖衍生物的高效合成

设计合成了2个Globo H四糖衍生物1和2, 将其作为标准样品可用于研究β1,3-葡萄糖醛酸(GlcA)转移酶及GlcA-3-O-硫酸化(Sulfo)转移酶在肿瘤组织内的特异性表达.     

Synthetic Studies on Sialoglycoconjugates 27: Synthesis of Sialyl-α(2→6)-Lewis X

ABSTRACT

Synthesis of a positional isomer of sialyl Lewis X with regard to the substitution of the terminal galactose residue of the pentasaccharide by N-acetylneuraminic acid is described. Dimethyl(methylthio)sulfonium triflate-promoted coupling of 2-(trimethylsilyl)ethyl O-(2,3,4-tri-O-benzyl-α-L-fucopyranosyl)-(1→3)-O-(2-acetamido-6-O-benzyl-2-deoxy-ß-D-glucopyranosyl)-(1→3)-O-(2,4,6-tri-O-benzyl-ß-D-galactopyranosyl)-(1→4)-2,3,6-tri-O-benzyl-ß-D-glucopyranoside (1) with methyl O-(methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosylonate)-(2→6)-2,4-di-O-benzoyl-3-O-benzyl-1-thio-ß-D-galactopyranoside (2) gave the desired hexasaccharide 3. Compound 3 was converted into the α-trichloro-acetimidate 6, via reductive removal of the benzyl groups, O-acetylation, removal of the 2-(trimethylsilyl)ethyl group, and treatment with trichloro-acetonitrile, which, on coupling with (2S, 3R, 4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol (7), gave the ß-glycoside 8. Finally, 8 was transformed, via selective reduction of the azide group, coupling with octadecanoic acid, O-deacylation, and hydrolysis of the methyl ester group, into the title ganglioside 11 in good yield.     

Carbohydrates as nucleophiles in conjugate addition for preparation of muramic acid analogues

Benzyl 2-acetamido-6-O-benzyl-3-O-[(S)-1-carboxy-isopropyl]-- -glucopyranoside (15) was synthesized stereoselectively by conjugate addition reaction, starting irom benzyl 2-acetamido-6-O-benzyl-2-deoxy--D-glucopyranoside (9) and crotonic acid ethyl ester under phase transfer conditions. The dipeptide L-Ala-D-Glu(OMe)OMe was coupled to 15 to give compuond 25 an analogue of the adjuvant active muramyl dipeptide (MDP)     

Acanmontanoside, a new phenylethanoid diglycoside from Acanthus montanus

A new phenylethanoid glycoside acylated with syringic acid, namely acanmontanoside, was isolated from the aerial portions of Acanthus montanus (Nees). T. Anderson, along with decaffeoylverbascoside, verbascoside, isoverbascoside, leucosceptoside A, (2R)-2-O-?-D-glucopyranosyl-2H-1,4-benzoxazin-3(4H)-one (HBOA-Glc), (2R)-2-O-?-D-glucopyranosyl-4-hydroxy-2H-1,4-benzoxazin-3(4H)-one (DIBOA-Glc), (3R)-1-octen-3-ol-3-O-?-D-xylopyranosyl-(1→6)-O-?-D-glucopyranoside and ebracteatoside B. The structure elucidations were based on physical data and spectroscopic analyses including 1D- and 2D-NMR.     

Synthesis of 2-acetamido-6-O-(2-acetamido-2-deoxy-β-D-glucopyranosyl)-2-deoxy-d-glucopyranose

Conclusion The synthesis of 2-acetamido-6-O-(2-acetamido-2-deoxy--D-glueopyranosyl)-2-deoxy-D-glucopyranose was accomplished.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 3, pp. 630–632, March, 1971.     

New phenolic constituents from the fruit juice of Phyllanthus emblica

Six new phenolic constituents, L-malic acid 2-O- (1), mucic acid 2-O- (5), mucic acid 1,4-lactone 2-O- (6), 5-O- (8), 3-O- (10), and 3,5-di-O- (11) gallates, were isolated from the fruit juice of Phyllanthus emblica together with their methyl esters (2-4, 7, 9), and their structures were determined by spectral and chemical methods. Compounds 5, 6, and 8, the major phenolic constituents of the juice, were present as an equilibrium mixture in aqueous solution.     

C3 cyclopolymerization. IV.1 Cationic polymerization of 1,3-bis(4-vinylnaphthyl) propane and the polymer structure yielded

The compound 1,3-bis(4-vinylnaphthyl)propane was prepared by a convenient dehydration of 1,3-bis[4-(1-hydroxyethyl)naphthyl]propane. The structure was confirmed by nuclear magnetic resonance (NMR) spectroscopy. The monomer was polymerized by antimony pentachloride, tin tetrachloride, titanium tetrachloride, or boron trifluoride etherate at 0°C in toluene, 1,2-dichloroethane, or a mixed solvent of 1,2-dichloroethane and nitromethane. Most of runs except for antimony pentachloride–catalyzed ones gave mainly benzene-soluble polymers. The structures of the polymers were studied by several spectroscopic methods. Comparison of NMR and fluorescence spectroscopic data of the polymers with those of syn-and anti-[3.3](1,4)napthalenophane was especially valuable in leading to the conclusion that they were cyclopolymers containing predominantly syn-[3.3]-(1,4)naphthalenophane units in the main chain.     

Synthetic Studies on Sialoglycoconjugates 18: Synthesis of 7-O-, 7,9-Di-O-, and 7,8,9-Tri-O-Acetyl-N-Acetyl-Neuraminic Acid Derivatives

ABSTRACT

7-O-, 7,9-Di-O-, and 7,8,9-tri-O-acetyl derivatives of N-acetyl-neuraminic acid were synthesized starting from benzyl [2-(trimethylsilyl)-ethyl 5-acetamido-3,5-dideoxy-8,9-O-isopropylidene-D-glycero-α-D-galacto-2-nonulopyranosid]onate (1).     

Synthesis of isomeric 1,3- and 1,4-bis[3(4)-nitrofuroxan-4(3)-yl]nitrobenzenes by nitration of the corresponding isomeric 1,3- and 1,4-bis[3(4)-nitrofuroxan-4(3)-yl]benzenes

Isomeric 1,3- and 1,4-bis[3(4)-nitrofuroxan-4(3)-yl]nitro(dinitro)benzenes were synthe-sized in high yields by nitration of the corresponding 1,3- and 1,4-bis[3(4)-nitrofuroxan-4(3)-yl]benzenes with a mixture of 100% nitric acid and concentrated sulfuric acid. The influence of 3- and 4-nitrofuroxanyl fragments on the regioselectivity of the nitration was revealed. The structure of 1,3-bis(4-nitrofuroxan-3-yl)-4-nitrobenzene was confirmed by X-ray diffraction analysis. 1,3- and 1,4-Bis(3-nitrofuroxan-4-yl)nitrobenzenes underwent thermal isomerization to more thermodynamically favorable 1,3- and 1,4-bis(4-nitrofuroxan-3-yl)nitrobenzenes.