铜蛋白质的配位化学模拟

概述了生物酶中铜蛋白质配位化学模拟的研究进展，介绍了铜离子配合物生物酶活性中心的重要铜蛋白质的结构与功能的研究方法及最新进展。     

血清中低分子量蛋白质的提取和鉴定

采用改进的圆盘凝胶电泳提取人血清中低分子量蛋白质, 去除了血清中分子量大于3×104的蛋白质, 将提取的低分子量蛋白质热变性后直接在溶液中酶解成肽, 经液相色谱-质谱分析, 并进行Mascot数据库检索, 确认出人血清中97种蛋白质.     

基于可断裂三功能探针的酪氨酸磷酸化蛋白质复合物的规模化分析

在细胞的信号转导过程中,磷酸化酪氨酸（Phosphotyrosine, pTyr）信号在许多通路中起着重要的调控作用。受pTyr信号调控的蛋白质复合物是信号传递早期过程中的关键分子机器,分析该类动态蛋白质复合物具有重要的意义。Photo-pTyr-scaffold是一种结合了化学探针与pTyr识别蛋白质结构域的化学蛋白质组学分析策略,采用该策略已经实现了对表皮生长因子受体（Epidermal growth factor receptor, EGFR）通路相关的pTyr信号蛋白质复合物的规模化分析。但是,该方法无法解析所鉴定复合物的一一对应关系,增加了后续复合物解析的复杂性。本研究在Photo-pTyr-scaffold探针设计的基础上,将可断裂基团引入至其生物素富集端,设计合成了新型的可断裂三功能探针,以实现对富集产物的可控洗脱。基于pTyr信号蛋白质复合物在化学交联后的分子量差异,利用十二烷基磺酸钠-聚丙烯酰胺凝胶电泳实现了对洗脱的pTyr蛋白质复合物的分离,进一步将不同分子量区域的蛋白质进行胶内酶解和质谱分析。理论上,发生化学交联的pTyr蛋白质复合物将在高于原蛋白质分子量的区域被...     

生命科学中的分析化学--蛋白质组分析

概述了分析化学在生命科学中的重要作用和蛋白质组分析的现状与展望。介绍了生物试样的制备、双向凝胶电泳分离蛋白质以及生物质谱鉴定蛋白质等蛋白质组分析的主要技术平台。     

电子束辐射固化环氧树脂的动态力学分析——树脂化学结构、分子量及其分布的影响

应用不同化学结构、分子量及其分布的环氧树脂进行了电子束辐射固化实验 ,对固化物进行了动态力学分析 ,研究了不同样品凝胶含量、内耗tanδ及动态模量的变化规律 .分析结果表明环氧树脂辐射反应活性与其化学结构有很大关系 ,酚醛型环氧树脂的辐射反应活性高 ,固化后高温模量及玻璃化温度较高 ,而脂环族环氧树脂反应活性小 .在低辐射剂量下 ,环氧树脂的固化度随分子量增大略有下降 ,但固化物的玻璃化温度随分子量增加而升高 .增大辐射剂量 ,树脂固化度的提高受分子量大小的影响很小 ,分子量较大样品的网络均匀程度有所提高 ,在较高反应程度下 ,玻璃化温度主要受固化度影响 .树脂固化程度也是决定其模量高低的主要因素 ,而在固化程度相近的情况下 ,分子量的影响作用很大 .在同样辐射剂量下 ,分子量分布宽的树脂固化反应程度高 ,但交联网络均匀性低 .     

基于多肽识别的电化学生物传感技术

多肽具有分子量小、易于合成、生物兼容性好、稳定性高及序列灵活多样等优点。因此,多肽作为新型生物识别元件,已被广泛应用于生物传感器的构建。电化学分析灵敏度高、准确度好、设备简单、检测范围广且易于操作。本文介绍了基于多肽识别的电化学生物传感器技术,包括多肽的修饰与固定化、多肽与待测物的识别及检测原理;综述了近五年多肽电化学生物传感器对重金属离子、小分子、蛋白质、细菌和病毒的检测;展望了肽基电化学生物传感器的发展趋势。     

位点特异、拓扑结构明确的蛋白质-聚氨基酸偶联物的简洁合成

发展位点特异且具有明确拓扑结构的蛋白质-高分子偶联物是高分子和化学生物学领域共同面对的挑战之一.在聚合物末端精确引入一个或多个具有特殊反应活性的生物正交官能团是实现"位点特异"生物偶联的关键前提.这一过程通常比较低效、需要多步骤的官能团转化、聚合后修饰以及保护脱保护,费时且繁琐.最近,通过在聚合过程中原位生成官能团,以一锅-两步的过程得到可直接用于蛋白质偶联的异遥爪聚合物,从而实现了多种不同拓扑结构的蛋白质-聚氨基酸偶联物的快速构筑.这一简洁的合成路线实现了以前尚未获得的头-尾相接的环状偶联物的制备,使这些偶联物表现出了很强的体外酶稳定性以及热稳定性.该工作是蛋白质-高分子偶联化学的一次创新的尝试;同时,利用该方法所制备的偶联物在蛋白质药物领域具有广阔的应用前景.     

在镉盐胁迫下扇贝鳃组织应激蛋白的研究

采用透射电子显微镜观察了虾夷盘扇贝(Patinopecten yessoensis)鳃组织细胞的超微结构, 发现镉盐能胁迫鳃组织中的腮丝、细胞核和线粒体产生病变. 利用双向凝胶电泳(2D-PAGE)优化分离扇贝鳃组织的全蛋白, 获得约800个蛋白质斑点, 并筛选出37个由于镉盐胁迫而产生的差异蛋白质斑点. 选用基质辅助激光解吸离子化-飞行时间质谱(MALDI-TOF MS)技术和数据库检索鉴定差异蛋白, 结果发现7个与镉毒性密切相关的蛋白质, 即热休克蛋白70和β-淀粉酶等上调蛋白质及原肌球蛋白、肌动蛋白和钙活化核苷酸酶1等下调蛋白质. 此外, 还发现转录调节子Crp/Fnr家族为低表达蛋白质, 而ABC转运子为高表达蛋白质. 在这些差异蛋白中, 部分蛋白质适合作为连续监测流动海水中镉污染程度及评价其危害性的蛋白指示物.     

腐植酸和黄腐酸结构研究

本工作对吐鲁番风化煤黄腐酸(FA)采用各种物理和化学方法(元素分析、官能团定量、紫外、红外、核磁共振、顺磁共振、凝胶过滤、凝胶电泳、等电聚焦、分子量测定等)进行了全面的结构表征。     

小分子α-螺旋模拟物

本文综述了近年来小分子α-螺旋模拟物的研究进展,介绍了α-螺旋结构在蛋白质相互作用中的重要性以及小分子α-螺旋模拟物在药物化学领域的应用。概括了联苯结构、酰胺结构、哒嗪结构及其他杂环结构小分子α-螺旋模拟物的最新进展,并介绍了小分子α-螺旋模拟物在蛋白质相互作用抑制剂方面的应用。总结了目前已有的小分子α-螺旋模拟物存在的一些不足之处,并对今后该研究领域的发展方向进行了展望。     

α-Amino acid derived enaminones and their application in the synthesis of N-protected methyl 5-substituted-4-hydroxypyrrole-3-carboxylates and other heterocycles

A new and simple synthesis of novel N-protected methyl 5-substituted-4-hydroxypyrrole-3-carboxylates, which exist in equilibrium with their 4-oxo tautomers, has been developed in two steps starting from N-protected α-amino acids. The key intermediates are enaminones, which can also be isolated, characterized, and used for the construction of other functionalized heterocycles, before they spontaneously decompose to pyrrole products. 4-Hydroxypyrroles are prone to partial aerial oxidation but can be efficiently alkylated or reduced to stable polysubstituted pyrrolidine derivatives.     

Specific intramolecular aromatic CH insertion of diazosulfonamides

The chemoselectivity in the intramolecular CH insertion of various diazosulfonamides has been experimentally studied. The results reveal that the aliphatic 1,4-, 1,5-, or 1,6-C(sp³)?H insertions of diazosulfonamides are not accessible, while the aromatic 1,5-C(sp²)?H insertion can be realized specifically by adjusting the diazo-adjacent group. In addition, the general chemoselectivities in the intramolecular CH insertions of diazosulfonyl compounds are summarized. Generally, diazosulfones undergo both aromatic 1,5-C(sp²)?H and aliphatic 1,5- and 1,6-C(sp³)?H insertions, while diazosulfonates undergo aliphatic 1,5- and 1,6-C(sp³)?H insertions. However, diazosulfonamides only undergo aromatic 1,5-C(sp²)?H insertion.     

N-Heterocyclic carbene-palladacyclic complexes: synthesis,characterization and their applications in the C-N coupling and α-arylation of ketones using aryl chlorides

N-Heterocyclic carbene-palladacyclic complexes 3 were successfully achieved in a one-pot procedure under mild conditions. The structure of 3a was unambiguously confirmed by X-ray single crystal diffraction and it was an active catalyst in the Buchwald-Hartwig amination and α-arylation of ketones even at very low catalyst loadings (0.01?mol%).     

Iodine-mediated oxidative Pictet-Spengler reaction using terminal alkyne as the 2-oxoaldehyde surrogate for the synthesis of 1-aroyl-β-carbolines and fused-nitrogen heterocycles

An efficient iodine-mediated oxidative Pictet-Spengler reaction in dimethyl sulphoxide (DMSO) using terminal alkynes as the 2-oxoaldehyde surrogate for the synthesis of aryl (9H-pyrido[3,4-b]indol-1-yl)methanones is described. The scope of the protocol includes the total synthesis of Fascaplysin, Eudistomins Y₁ and Y₂. The methodology is extended for preparing pyrrolo[1,2-a]-quinoxaline and indolo[1,5-a]quinoxaline derivatives. The utility of 1-aroyl-β-carbolines was demonstrated by performing palladium-catalyzed β-carboline directed ortho-C(sp2)-H functionalization of the phenyl ring with thiomethyl (SMe) group using DMSO as source and for accessing 4-aryl-canthin-6-ones.     

Facile synthesis of bicyclic 1-arylpyrazol-5-ones

In this Letter, we described a facile method for constructing fused bicyclic 1-arylpyrazol-5-one ring system. We employed various methylene-containing carboxylic acids as the substrates and proved that the pyrazolone ring closure requires activated methylene group in intermediate II. Accordingly, a series of structurally diversified, fused bicyclic 1-arylpyrazol-5-ones was prepared in moderate to high yields using the requisite substrates.     

Synthesis of pyrrolo[1,2-a]pyrazines and pyrazino[1,2-a]indoles by Curtius reaction in Morita-Baylis-Hillman derivatives

Synthesis of substituted pyrrolo[1,2-a]pyrazines and pyrazino[1,2-a]indoles from the Morita-Baylis-Hillman derivatives of acrylates via saponification followed by Curtius reaction is described.     

正丁胺对激光染料荧光谱影响的研究

用正丁胺作为碳源,采用射频辉光放电制备碳膜,选用激光染料R6G和聚乙二醇混合液作为蒸气源,采用单源热蒸发,在蒸发室与染料同时沉积得到混合膜,用拉曼光谱和红外光谱分析了碳膜的结构和键合方式,分析表明:碳膜中存在胺基团和氢原子.混合膜的荧光谱测量结果表明,认为正丁胺对染料荧光谱的影响是因为胺基和氢原子的存在.     

Cu0-catalysed 1,3-dipolar cycloadditions of α-amino acid derived N,N-cyclic azomethine imines to ynones

A series of 20 CuAIAC reactions between eight 4-acylamino substituted pyrazolidine-3-one-1-azomethine imines and four terminal ynones were performed using Cu⁰ as catalyst. The corresponding fluorescent cycloadducts were obtained in very high yields upon simple workup. Thus, Cu-metal turned out to be a better catalyst than Cu^I in terms of yield and ease of isolation. Availability of azomethine imines, mild reaction conditions, and simple workup enable a “click” access to libraries of densely substituted 2,3-dihydro-1H,5H-pyrazolo[1,2-a]pyrazol-1-ones. Reactivity of differently substituted dipoles was evaluated experimentally and by quantum chemical methods (DFT).     

Synthesis and antioxidative/anti-inflammatory activity of novel fullerene–polyamine conjugates

(E)-4-(Fullerenopyrrolidin-1-yl)-3-methylbut-2-enoic acid and its corresponding succinimidyl ester, readily obtained through Prato-type modification of C₆₀, were used for the selective N-acylation of polyamines. The thus obtained conjugates were evaluated for their antioxidative and anti-inflammatory activity and their cytotoxicity was determined. Members of this family of compounds showed interesting anti-lipid peroxidation, anti-lipoxygenase and anti-inflammatory activity and comparable cytocompatibility to spermidine.