卤代二苯乙烯体系中卤-卤相互作用的调控及其对分子聚集态和发光特性的影响

卤素-卤素(X···X)相互作用是一类强的分子间相互作用,这种非共价键分子间的相互作用对有机π分子的聚集态结构和光电特性具有重要的影响.本文通过在反式二苯乙烯类化合物骨架上引入给电子基团甲硫基和调节卤素取代基的位置,实现了分子间卤素-卤素相互作用的可控构筑,并进一步研究了卤素-卤素相互作用对卤代反式二苯乙烯类分子聚集态和发光特性的影响.该实验结果为调控有机π分子聚集态结构,获得高性能有机光电材料提供了新思路.     

核酸适体偶联药物的生物偶联构建技术与应用

核酸适体被称为“化学抗体”, 具有与抗体类似或更加优异的特异性和亲和力, 可以精准地靶向靶蛋白, 与靶蛋白特异性结合. 此外, 核酸适体还具有获取简单、 合成简便、 易于进行化学修饰、 不易变性、 靶标范围广、 免疫原性低及细胞内化快等优点, 已被广泛应用于众多研究领域. 在癌症治疗领域, 核酸适体作为一种优异的靶向识别工具和药物递送载体, 可实现抗肿瘤药物的精准递送. 将核酸适体与药物分子偶联, 可通过核酸适体的靶向作用使药物分子随核酸适体共同进入靶细胞, 实现药物分子在靶细胞内的富集, 进而促进靶细胞的死亡. 近年来, 核酸适体偶联药物已成为癌症靶向治疗的前沿新兴领域, 希望通过该领域的深入研究为癌症靶向治疗领域提供新思路. 本文综合评述了以生物偶联技术构建的核酸适体偶联药物及其应用研究.     

DNA与其靶向分子相互作用研究进展

DNA与其靶向分子相互作用的研究不仅对阐述一些抗肿瘤、抗病毒药物及致癌物的作用机理,而且对进一步指导人工核酸酶的合成及DNA高级结构研究等方面的工作都具有重要意义.本文着重评述了近年来不同结构类型的DNA靶向分子与DNA相互作用研究方面的进展.     

偶氮苯作用的核酸开关在生物体内的可逆光调控

随着人们对偶氮苯分子光异构化机理和特性认识的深入,偶氮苯在核酸分子中的引入及其相关过程的可逆调控也受到了大量关注.偶氮苯分子作为光响应元件不仅用于合成智能材料或分子机器,而且正迅速渗透到化学生物学体系的分析和调控.考虑到核酸分子包含的信息多样性,小分子偶氮化合物引入到核酸分子中,可实现开关核酸的结构、RNA沉默、基因表达、适配体识别、酶活性等,也可用作核酸探针了解结构信息和分子之间的作用机理.因而,功能核酸的光可逆调控及其在生物领域中的应用,成为核酸化学领域的热门课题.本文主要阐述了偶氮苯与核酸结合的4种不同方式的设计原理及特点,通过筛选一些有代表性的例子,介绍偶氮苯类光敏分子的光异构化性能及其对核酸结构和功能的可逆调控在生物领域的研究进展,并列举出现阶段可能存在的问题,及对未来的发展前景进行展望.     

具有核酸分子"光开关"特性钌(Ⅱ)配合物的研究进展

钌（Ⅱ）配合物类核酸分子“光开关”探针性质稳定、无毒环保,可用于痕量核酸检测、基因序列分析及三链DNA检测、DNA图像研究及DNA动力学过程分析、基因损伤研究、基因转染材料研究、量子点生物效应研究及用作电化学探针。随着核酸及其相关分析研究的不断深入和适配子技术的迅猛发展,基于核酸和核酸分子“光开关”还可进行药物筛选、生命活性分子如ATP及蛋白质等的分析检测,具有简便、快速、灵敏、抗光漂白等特性。对生命科学基础研究、食品安全及医学诊断具有重要的理论意义。作者对近10年来核酸分子“光开关”探针研究进展进行了评述,引用文献55篇。     

"Hofmann-Löffler-Freytag"型反应合成吡咯烷类化合物的研究进展

含氮杂环化合物广泛存在于天然产物及人工合成的分子中,且表现出很高的生物活性。其中吡咯烷类衍生物是天然产物及药物分子中的特定结构单元,引起了化学家们的广泛关注。发展简洁、高效、普适性强的方法构建该类化合物一直是有机化学家所追求的目标。本文综述了霍夫曼-勒夫勒-弗赖伊塔格(Hofmann-L?ffler-Freytag,简称HLF)反应在合成吡咯烷类化合物中的研究进展,内容主要包含两部分:1)卤素介导的HLF型反应;2)无卤素介导的HLF型反应。     

手性不对称脲联苯二甲酸分子钳的设计合成

以联苯二甲酸为隔离基,手性不对称脲为手臂,设计合成了一类新型的手性分子钳。4个分子钳均为新化合物,其结构均经1H NMR,IR,MS和元素分析所确证,并且考察了其对卤素阴离子Cl-、Br-、I-的识别性能。初步的实验结果表明,这类分子钳不仅可与所考察的卤素阴离子形成1:1型超分子配合物,而且对卤素阴离子具有良好的识别选择性,识别选择性为I->>C l->B r-。     

超卤素的结构、特性及应用研究进展

卤族(halogen)元素,包括氟(F)、氯(Cl)、溴(Br)、碘(I)和砹(At),具有高的电子亲和能(EA)与强反应活性及氧化性.它们在材料合成与改性方面的广泛应用极大地激励人们研究超卤素(superhalogen),即EA比卤素原子的EA(3.0～3.6eV)更高的一类基团或分子.与卤素原子相比,超卤素表现出电负性更大、结构更丰富、性质更新颖等更加丰富的特征.本文总结了最近30年来人们在设计与合成新型超卤素和飙卤素(hyperhalogen)方面所取得的实验和理论研究进展,讨论了超卤素和飙卤素的电子结构和物性,展望了超卤素在开发新型磁性材料、环境净化材料、高能密度材料以及非线性光学材料等方面的应用前景.     

聚苯乙烯类发光材料研究进展

高分子发光材料具有良好的溶液加工特性,是发展低成本、大面积平板显示和固体照明器件的重要基础材料。聚苯乙烯类发光材料在合成方法上具有聚合方法简单、无需使用催化剂、无卤素原子残留等优势,在化学结构上具有非共轭主链结构和易于引入功能化侧链等特点,在发光特性上具有宽带隙特征,近年来发展成为一类重要的高分子发光材料。本文从材料和器件角度,围绕聚苯乙烯类荧光材料、聚苯乙烯类磷光材料和聚苯乙烯类热活化延迟荧光材料的分子设计和电致发光性能,综述了聚苯乙烯类发光材料的研究进展,分析总结了其未来发展所面临的机遇和挑战。     

卤素及三卤甲基侧取代氮、硫杂冠化合物的电子结构

用ＡＭ１ 方法计算了２０ 个卤素及三卤甲基侧取代氮、硫杂冠化合物分子的电子结构。结果表明,这类杂冠化合物分子的总能量,最高占据分子轨道能量,杂冠醚环中氧、氮原子的电荷分布和空腔大小呈现出一定的规律性。它们对于络合过渡金属具有较强的选择性。     

Influence of halogenation on the properties of uracil and its noncovalent interactions with alkali metal ions. Threshold collision-induced dissociation and theoretical studies

The influence of halogenation on the properties of uracil and its noncovalent interactions with alkali metal ions is investigated both experimentally and theoretically. Bond dissociation energies of alkali metal ion-halouracil complexes, M+(XU), are determined using threshold collision-induced dissociation techniques in a guided ion beam mass spectrometer, where M+ = Li+, Na+, and K+ and XU = 5-fluorouracil, 5-chlorouracil, 6-chlorouracil, 5-bromouracil, and 5-iodouracil. The structures and theoretical bond dissociation energies of these complexes are determined from ab initio calculations. Theoretical calculations are also performed to examine the influence of halogenation on the acidities, proton affinities, and Watson-Crick base pairing energies. Halogenation of uracil is found to produce a decrease in the proton affinity, an increase in the alkali metal ion binding affinities, an increase in the acidity, and stabilization of the A::U base pair. In addition, alkali metal ion binding is expected to lead to an increase in the stability of nucleic acids by reducing the charge on the nucleic acid in a zwitterion effect as well as through additional noncovalent interactions between the alkali metal ion and the nucleobases.     

基于自动磁珠转运的转基因蛋白Cry1Ab检测

基于自动磁珠转运,建立了转基因蛋白Cry1Ab免疫检测的新方法.利用水热法制备了粒径约400 nm的纳米磁球,并进行电镜表征,通过溶胶法对磁球表面进行氨基修饰,采用戊二醛偶联对磁珠实现抗体包被,在核酸提取仪中进行酶联免疫反应,采用分光光度法进行检测.本方法对转基因蛋白Cry1Ab的检出限低于1 μg/L,与商品化酶联免...     

RESISTANCE OF THE SCRAPIE AGENT TO INACTIVATION BY PSORALENS

–In searching for a nucleic acid within the scrapie agent, we employed psoralens which penetrate the coats of most conventional viruses, form photoadducts with their genomes, and block replication of the viruses. Five psoralens, at concentrations up to 500 times greater than those required to inactivate conventional viruses, did not influence scrapie agent titers in partially purified preparations from murine spleen and hamster brain. ³H-psoralens were used to monitor the formation of photoadducts within nucleic acid standards added to preparations of the scrapie agent. Since no inhibition of psoralen photoadduct formation was observed in these preparations, one of three possibilities seems likely: the scrapie agent is devoid of nucleic acid, the psoralens failed to penetrate the protein coat of the agent, or its nucleic acid is unreactive with psoralens.     

Effects of Six‐Membered Carbohydrate Rings on Structure,Stability, and Kinetics of G‐Quadruplexes

We have evaluated the conformational, thermal, and kinetic properties of d(TGGGGT) analogues with one or five of the ribose nucleotides replaced with the carbohydrate residues hexitol nucleic acid (HNA), cyclohexenyl nucleic acid (CeNA), or altritol nucleic acid (ANA). All of the modified oligonucleotides formed G‐quadruplexes, but substitution with the six‐membered rings resulted in a mixture of G‐quadruplex structures. UV and CD melting analyses showed that the structure formed by d(TGGGGT) modified with HNA was stabilized whereas that modified with CeNA was destabilized, relative to the structure formed by the unmodified oligonucleotide. Substitution at the fourth base of the G‐tract with ANA resulted in a greater stabilization effect than substitution at the first G residue; substitution with five ANA residues resulted in significant stabilization of the G‐quadruplex. A single substitution with CeNA at the first base of the G‐tract or five substitutions with HNA resulted in striking deceleration or acceleration of G‐quadruplex formation, respectively. Our results shed light on the effect of the sugar moiety on the properties of G‐quadruplex structures.     

Bridging the gap between proteins and nucleic acids: a metal-independent RNAseA mimic with two protein-like functionalities.

Two synthetically modified nucleoside triphosphate analogues (adenosine modified with an imidazole and uridine modified with a cationic amine) are enzymatically polymerized in tandem along a degenerate DNA library for the combinatorial selection of an RNAse A mimic. The selected activity is consistent with both electrostatic and general acid/base catalysis at physiological pH in the absence of divalent metal cations. The simultaneous use of two modified nucleotides to enrich the catalytic repertoire of DNA-based catalysts has never before been demonstrated and evidence of general acid/base catalysis at pH 7.4 for a DNAzyme has never been previously observed in the absence of a divalent metal cation or added cofactor. This work illustrates how the incorporation of protein-like functionalities in nucleic acids can bridge the gap between proteins and oligonucleotides underscoring the potential for using nucleic acid scaffolds in the development of new materials and improved catalysts for use in chemistry and medicine.     

Enzymatic Synthesis of Sequence‐Defined Synthetic Nucleic Acid Polymers with Diverse Functional Groups

The development and in‐depth analysis of T4 DNA ligase‐catalyzed DNA templated oligonucleotide polymerization toward the generation of diversely functionalized nucleic acid polymers is described. The NNNNT codon set enables low codon bias, high fidelity, and high efficiency for the polymerization of ANNNN libraries comprising various functional groups. The robustness of the method was highlighted in the copolymerization of a 256‐membered ANNNN library comprising 16 sub‐libraries modified with different functional groups. This enabled the generation of diversely functionalized synthetic nucleic acid polymer libraries with 93.8 % fidelity. This process should find ready application in DNA nanotechnology, DNA computing, and in vitro evolution of functional nucleic acid polymers.     

三嗪树脂对生物碱的分子识别研究

合成了丙烯腈-二乙烯苯交联共聚物,对其进行化学修饰得到二氨基三嗪树脂.尝试了该三嗪树脂对脲嘧啶和胸腺嘧啶在甲醇中的吸附情况,初步研究了该三嗪树脂在质子性溶剂中对生物碱的分子识别作用.     

Study on suitability of KOD DNA polymerase for enzymatic production of artificial nucleic acids using base/sugar modified nucleoside triphosphates

Recently, KOD and its related DNA polymerases have been used for preparing various modified nucleic acids, including not only base-modified nucleic acids, but also sugar-modified ones, such as bridged/locked nucleic acid (BNA/LNA) which would be promising candidates for nucleic acid drugs. However, thus far, reasons for the effectiveness of KOD DNA polymerase for such purposes have not been clearly elucidated. Therefore, using mutated KOD DNA polymerases, we studied here their catalytic properties upon enzymatic incorporation of nucleotide analogues with base/sugar modifications. Experimental data indicate that their characteristic kinetic properties enabled incorporation of various modified nucleotides. Among those KOD mutants, one achieved efficient successive incorporation of bridged nucleotides with a 2'-ONHCH?CH?-4' linkage. In this study, the characteristic kinetic properties of KOD DNA polymerase for modified nucleoside triphosphates were shown, and the effectiveness of genetic engineering in improvement of the enzyme for modified nucleotide polymerization has been demonstrated.     

Chitosan/Ionic Liquid Composite Electrode for Electrochemical Monitoring of the Surface‐Confined Interaction Between Mitomycin C and DNA

In the present study a chitosan/ionic liquid modified pencil graphite electrode (CHIT‐IL‐PGEs) was developed for the first time for enhanced electrochemical monitoring of nucleic acid, and the interaction of the anticancer drug Mitomycin C (MC) and calf thymus double stranded DNA (dsDNA) by measuring the oxidation signals of MC and guanine in the same voltammetric scale. Differential pulse voltammetry, cyclic voltammetry and electrochemical impedance spectroscopy techniques were used to evaluate the performance of the CHIT‐IL based biosensor on electrochemical monitoring of DNA, and drug‐DNA interaction. The experimental parameters, IL, dsDNA and MC concentration and the interaction time were then optimized.