核酸探针及其在生物分析中的应用

核酸探针由于具有结构可变,合成简单和易于修饰等特点,被广泛应用于酶、蛋白质、生物小分子、金属离子、核酸以及细胞等生物分析物的检测,成为生物分析领域中不可或缺的一种研究工具。基于核酸探针发展起来的核酸信号放大策略为检测低丰度的物质提供了重要平台,提高了核酸探针检测的灵敏度,对于生物医学研究,分子诊断和药物基因组学至关重要。对核酸探针的类型、核酸信号放大方法以及核酸探针在生物分析领域的应用进行了介绍,对核酸探针的发展进行了总结与展望。     

DNA发夹结构自组装信号放大策略应用的研究进展

DNA发夹结构自组装因具有无酶参与、等温以及识别序列能力强等优点,在生物分子和金属离子检测方面展现了良好的发展前景。该文梳理了DNA发夹结构自组装信号放大策略的类型,综述了近年来该策略在致病菌、核酸肿瘤标记物、蛋白质、无机金属离子,以及生物小分子检测中应用的研究进展,并对其未来发展趋势进行了展望,旨在为基于DNA发夹结构自组装检测生物分子提供一定的参考。     

核酸等温扩增技术在电化学生物传感器中的应用

生物分子检测在临床诊断、基因治疗、基因突变分析等方面变得日益重要,因而,建立简单、快速、灵敏的检测方法具有重要意义。近年,电化学生物传感器因其简单、便携、易操作、成本低等优势在生物分子检测的研究中备受关注。为了提高检测方法的灵敏度,不同的核酸等温扩增技术被应用于电化学生物传感器的构建中。本文简单介绍了电化学生物传感器的工作原理,着重综述了几种主要应用于电化学传感器中的核酸等温扩增技术,同时比较了各方法的优缺点。     

基于核酸探针的光学传感方法和细胞成像研究

许多疾病的特征在于各种生物分子表现出的异常活性,这些物质通常在细胞内外显示过表达现象,因此对其灵敏靶向识别可以提供诊断和治疗效用。由于基因诊疗和化学传感技术的发展,用于灵敏检测细胞内外生物化学物质的核酸探针突显优势。核酸探针可以在稳定进入细胞的同时,特异性地结合目标物质,通过光学方法检测或通过成像技术标识出来。本文综述了采用光学传感方法和成像技术,基于核酸探针检测生物分子的新进展。根据检测对象进行分类,概括分析了几个代表性体系:核酸序列、蛋白质和酶、化学物质和物理化学条件,并详细阐述其关键设计原理、灵敏度及样品检测等结果,同时指出了各类核酸探针的优缺点。     

生物电分析新方法与技术研究及仪器研制

生物电分析化学是一门利用生物分子作为识别元件、通过生物反应后电极过程产生的信号的变化对未知物质进行定性、定量分析的学科.目前常用的生物识别元件有酶、核酸(包括核酸适配体)、抗体、受体等,而可供检测的信号广义上包括电流、电阻、光电流和电化学发光等.在过去5年的工作中,我们针对生命科学、临床检验和环境监测等实际应用领域,分别研究了电化学酶传感器、光电化学核酸损伤传感器和电化学发光免疫检测的原理与技术,并研制了相应的检测仪器.     

基于核酸适配体的生物标志物检测方法研究进展

核酸适配体是指能与特定靶分子结合的寡核苷酸链。因其具有易修饰、易合成和低免疫原性等特点,作为生物传感器的靶向元件,已广泛应用于各种生物标志物检测技术中。本文综述了近年来基于核酸适配体的生物标志物的检测技术在癌症、心血管疾病、阿尔兹海默症、抑郁症等多个疾病领域的诊断研究进展,列举核酸适配体新兴技术的创新应用,以期为生物标志物的检测提供新思路,也有望为相关疾病的早期诊断和治疗提供参考。     

生物膜层干涉技术在生物分子分析和检测中应用的研究进展

生物膜层干涉技术是基于光干涉信号实现对生物分子动力学分析或快速检测的非标记分析检测技术。因具有实时提供分析物信息、分析速度快和样品耗量少等优点,该技术已被应用于蛋白质、核酸、脂质、糖类及其他生物分子之间相互作用的分析;所需样品量少、特异性强等优点也为该技术应用于快速检测奠定了基础。该文介绍了生物膜层干涉技术的基本原理,综述了其在动力学分析和快速检测领域的相关应用研究,并对其发展趋势和应用前景进行了展望。     

核酸工具酶辅助的金属稳定同位素标记方法在生物分析中的应用

本文主要概述了近年来核酸工具酶辅助的基于金属稳定同位素标记的电感耦合等离子体质谱(ICP-MS)检测方法在生物分析中的发展和应用,简要介绍了该方法在蛋白质、核酸及一些生物小分子检测中的应用。最后对核酸工具酶辅助的基于金属稳定同位素标记的电感耦合等离子体质谱(ICP-MS)检测方法的发展前景做了展望。     

核酸介导信号放大光学生物传感器在食品污染物检测中的应用EI北大核心CSCD

信号放大是新型生物传感分析过程中重要的环节。核酸介导的信号放大技术凭借核酸材料灵活的结构设计、低成本和易于制备等特点,在生物传感快速检测技术的开发上逐渐发展成为一项重要的分支,广泛应用于食品、环境和医药等新型检测方法开发。介绍了传统和新型核酸扩增技术、生物条形码和DNA walker等信号放大机理和应用,同时进一步综述核酸信号放大技术结合光学生物传感在食品污染物中检测的应用,如化学污染物、毒素类污染物、和重金属污染物等,并对核酸介导的信号放大技术在食品污染物检测中的问题和前景进行讨论。     

固相纳米孔对核酸组装的“免标记、均相”表征和应用探索

随着核酸自组装领域的飞速发展,除了作为遗传信息的载体外,核酸成为了一种具有高操作自由度和无限可能性的功能材料.基于核酸自组装原理的DNA纳米技术凭借其强大的可编辑性已经广泛应用于生物传感、纳米材料工程、医学诊疗以及分子计算机等领域.纳米孔作为一种新兴的单分子分析技术具有高分辨、高通量、免标记等特点,近年来在基因测序、分子物理化学性质分析等领域展示出了极大的应用潜力.作为一种新型高分辨表征技术,纳米孔已经在DNA纳米技术研究中崭露头角,被用于原位追踪和分析核酸分子的自组装行为.另一方面,DNA纳米技术也为纳米孔传感所面临的技术瓶颈提供了更多样化的解决思路,如借助功能核酸(Aptamer或DNAzyme)和无酶扩增核酸分子线路实现纳米孔对待测物的特异性增敏检测.本专论旨在通过对近期纳米孔技术与核酸自组装的跨领域研究成果进行系统性回顾,总结并展望纳米孔传感领域内核酸自组装的研究进展,以期为单分子生物分析、信息检索、基因分型和临床诊断等领域提供新思路和新方法.     

二氧化碳和丙烯直接合成甲基丙烯酸的NiPMo/TiO2催化剂的研究

用溶胶-凝胶法以磷钼酸(MPA)的镍盐溶液水解钛酸四丁酯制备了NiPMo/TiO2催化剂.使用ICP、 XRD、 TG-DTA、 IR、 TPD-MS和微反应技术研究了催化剂的化学组成、热稳定性、化学吸附性质和催化反应性能.杂多钼酸盐与TiO2通过O2-在TiO2表面发生了键合.在623 K下,杂多阴离子仍保持原有的Keggin结构.CO2在Lewis酸位Ni(Ⅱ)和Lewis碱位Ni-O-Mo的桥氧协同作用下生成CO2卧式吸附态Ni(Ⅱ)←O-(CO)←(O--Ni).丙烯有多种吸附态在催化剂上吸附.在563 K、 1 MPa和空速1500 h-1的反应条件下,丙烯的摩尔转化率为3.2%,产物MAA选择性为95%.     

Synthesis of 1-benzyloxypyrazin-2(1H)-one derivatives

Different approaches for the synthesis of 1-benzyloxypyrazin-2(1H)-one derivatives from simple amino acids have been investigated. A library of 33 precursors for the preparation of N-hydroxy pyrazinones was obtained in moderate to good yields.     

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.     

A general and convenient synthesis of 4-(tosylmethyl)semicarbazones and their use in amidoalkylation of hydrogen,heteroatom, and carbon nucleophiles

A general synthesis of previously unknown semicarbazone-based α-amidoalkylating reagents, 4-(tosylmethyl)semicarbazones, has been developed. The synthesis involved three-component condensation of semicarbazones of aliphatic or aromatic aldehydes with the same or other aldehydes and p-toluenesulfinic acid. The scope and limitations of this reaction were investigated. The compounds obtained were demonstrated to be an efficient α-(4-semicarbazono)alkylating agents. They were reacted with H- (sodium borohydride), O- (sodium methylate), S- (sodium phenylthiolate), N- (pyrrolidine, sodium succinimide), P- (trialkyl phosphites), and C-nucleophiles (sodium diethyl malonate) to give the corresponding products of the tosyl group substitution, 4-substituted semicarbazones, including analogues of nitrofurazone. Among the prepared compounds tested in vitro for antibacterial and antifungal activity, three nitrofuryl-containing semicarbazones exhibited high biological activities with minimum inhibitory concentration (MIC) values of 8–32 μg/mL.     

Toward new camptothecins. Part 6: Synthesis of crucial ketones and their use in Friedländer reaction

In the context of the preparation of camptothecin and luotonin A analogs, the synthesis of some key keto-precursors and their use in Friedländer condensation are described. This paper also focuses on the stability of these keto intermediates and emphasizes the major differences between indolizinones and pyrroloquinazolinones series. Noteworthy is also the report of some original structures isolated as by-products of some experiments.     

Synthesis of novel chiral bidentate hydroxyalkyl-N-heterocyclic carbene ligands and their application in palladium-catalyzed Mizoroki–Heck couplings and asymmetric addition of diethylzinc to benzaldehyde

A small library of new chiral bidentate hydroxyalkyl-imidazolium salts 1 is conveniently synthesized on multi-gram scale from inexpensive and commercially available chiral pool amino acids. The corresponding carbenes, generated by deprotonation of imidazolium salts 1, in combination with palladium(II) chloride were tested in the Mizoroki–Heck coupling reaction. The most significant results in terms of yields and reactivities were achieved with low catalyst loading. The catalytic activities of these imidazolium salts were also investigated in the asymmetric addition of diethylzinc to benzaldehyde. The use of MgO nanoparticles as an additive in conjunction with these ligands played a crucial role in increasing the efficiency of these reactions.     

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.