原子力显微镜对细胞色素C分子结构的形态研究

用原子力显微镜(AFM)对不同浓度下细胞色素C的分子形态,以及加入蛋白质降聚和变性剂脲后的形态变化进行了考察。实验结果显示,在50μmol/L的低浓度溶液中细胞色素C分子主要以直径为3nm的类球形单体形式存在。浓度增大,细胞色素C分子发生聚集,且随着浓度的进一步增大,细胞色素C分子倾向于形成更大的聚集体。浓度为200μmol/L时,聚集体分子间相互缠绕,形成链状结构。浓度低于0.8mol/L的脲的加入基本不影响细胞色素C分子的形态。加入较高浓度的脲,细胞色素C聚集体的聚集数降低,聚集体分子间没有明显的链状结构。     

基于超分子化学的核酸表观遗传修饰研究

核酸是生物体的遗传物质,在生命体系中发挥着重要作用.除了构成核酸的经典碱基之外,核酸中还存在天然修饰的碱基,这被称为核酸的表观遗传修饰.核酸的表观遗传修饰在基因表达过程中具有重要的调控作用,对生物体遗传和生命生长过程影响很大,并且核酸表观遗传与疾病密切相关.超分子化学是研究分子间键的化学,而许多生物分子都需要通过超分子化学作用来发挥其生物功能,可以说生物体内天然存在着大量的超分子化学过程.本文综合评述了基于超分子化学的核酸表观遗传修饰研究的一些代表性工作.     

基于蛋白质骨架的人工水解酶的理性设计

蛋白质是生命体的重要组成部分,其中生物酶在生命体系中发挥至关重要的作用。蛋白质分子设计是研究生物酶结构与功能关系的重要手段。本文综述了基于蛋白质骨架的人工水解酶的理性设计与功能研究进展,包括对天然蛋白的重新利用和重新改造,基于3-股螺旋、4-股螺旋或锌指蛋白的分子设计,以及血红蛋白(如细胞色素b₅和肌红蛋白突变体)水解酶催化活性的调控等,阐明了人工水解酶分子设计的基本思路与研究方法,为合理构建人工水解酶或其他生物酶提供了重要的信息。人工水解酶的理性设计进展,不但深化我们对天然酶结构-性质-反应-功能关系的认识,而且还提升我们创造具有优越功能的人工生物酶的能力。     

基于功能核酸的细胞荧光成像

细胞是生物体基本的结构和功能单元,对活细胞中特定生物组分进行动态分析,将为相关生命活动过程的研究提供重要信息。荧光成像为细胞分析提供了一种操作简单、灵敏度高、可实时监测细胞微观动态分子过程的光学生物成像技术。发展高性能的荧光探针用于活细胞成像已成为研究热点。功能核酸是一类具有特殊化学和生物学功能的寡核苷酸分子,除了天然存在的核酶(Ribozyme)和核糖开关(Riboswitch)之外,还包括通过指数富集的配体系统进化技术(SELEX)筛选获得的核酸适体和脱氧核酶(DNAzyme)。功能核酸由于具有合成简单、免疫原性低、相对分子质量小、化学稳定性高、易于修饰等优点,在生物成像领域受到广泛关注。本文主要综述了基于功能核酸的荧光探针在细胞成像领域中的应用研究,总结了该领域面临的挑战,并对其未来发展方向进行了展望。     

酶性核糖核酸

核酸(脱氧核糖核酸(DNA )及核糖核酸(RNA))和蛋白质都是重要的生命基础物质,是维持生命机器正常运转的最重要的物质基础。核酸是信息分子,担负着遗传信息的贮存、传递及表达等基本生物功能。蛋白质是功能分子.表现遗传性状、执行各种生物机能;特别是生物细胞内的各种化学过程,只有依靠蛋白质(酶)的参与才能在极温和的条件下     

细胞分泌物中的聚糖分析

聚糖是细胞的一种重要组成物质,主要由单糖、寡糖或者多糖组成.它们与蛋白质或脂质相连接,形成糖缀合物.聚糖结构的多样性决定了糖缀合物包含丰富的关于细胞和疾病状态的信息.因此,细胞分泌的聚糖分析对细胞以及疾病状态的监测具有重要意义.基于在细胞外聚糖的相关研究,综述了细胞分泌聚糖的类型、生物功能和生物学意义,并重点归纳了细胞分泌聚糖的识别方法和检测技术,展望了细胞分泌物中聚糖分析的前景.     

蛋白质氮连接聚糖的化学合成研究进展

糖是自然界种类最丰富、结构最多样的一类生物分子,参与了许多重要的生命过程.糖在生物体内通常以糖脂、糖蛋白等缀合物的形式存在,发挥着十分重要的生物学作用.氮连接聚糖(N-linked glycan)是糖蛋白的重要组成部分,但是在自然界中通常以微观非均一的形式存在,均一结构的糖链难以获取,这极大地阻碍了糖科学的相关研究.化学合成是获取均一结构聚糖、进而用以研究其生物学功能的重要手段.本综述着重总结了通过化学方法制备真核蛋白质中最为常见的一类糖链——复杂型氮连接聚糖的最新研究进展.     

用于肝细胞球形聚集体培养的生物材料*

在进行与肝脏疾病治疗的相关研究中,肝细胞的体外培养是一个关键的问题。由于微环境的变化,肝细胞容易在体外培养中逐渐丧失正常表型和肝特异性功能。研究发现,在适当条件下,肝细胞可以形成多细胞球形聚集体,肝细胞在球形聚集体中呈现出与体内形态相仿的立体结构,细胞的表型和功能都得到了较好的维持。因此,如何调控肝细胞球形聚集体的形成以及尺寸形貌,得到具有高细胞密度、能在体外长时间保持高水平肝特异性功能的肝细胞球形聚集体是这方面研究的热点。本文对近年来肝细胞球形聚集体培养的研究成果进行了综述。首先介绍了肝细胞在体内的生长环境和肝脏的细胞结构,然后对培养肝细胞的生物材料各方面的性质,如材料的化学组成、表面电荷、亲疏水性质、表面形貌以及立体结构对肝细胞球形聚集体的影响进行了阐述。同时也简要介绍了其他一些因素对肝细胞球形聚集体培养的影响。最后,对肝细胞球形聚集体培养的研究进展进行了总结和展望。     

化学生物学中光敏分子微阵列的表面构建与应用

分子微阵列是有机合成（特别是组合化学合成）方法应用于生物和医学研究而发展起来的高科技集成技术,通过把微电子、微加工技术和有机化学合成反应相结合,在固体基质（如硅片、玻片、瓷片等）表面构建微型的生物有机化学分子系统,以实现对细胞、蛋白质、核酸及其他生物组分进行快速、敏感、高效地处理．近年来,随着表面化学构建策略研究的不断深入和迅猛发展,分子微阵列技术的应用领域不断拓展,已从最初用于核酸分子的杂交测序延伸到基因组功能研究的各个方面．本文着重综述了光敏分子微阵列的表面化学构建策略研究及其在化学生物学分析中应用的最新进展,并展望了其发展的未来趋势．内容主要包括：小分子与多肽分子微阵列、蛋白质分子微阵列、核酸分子微阵列和糖分子微阵列等．     

环状寡聚核苷酸的研究进展

环状结构的核酸因其首尾相连的特殊结构,可提高其对核酸外切酶的稳定性,并且其环状结构可使其具有特殊的功能.早期由于检测技术的限制,研究者对环状核酸的研究相对较少.近年来,随着科学技术的进步,研究者发现生物体内存在各种环状核酸,并具有独特的生理调节功能.对于较小的环状寡聚核苷酸(几十个碱基)在生命体中是否存在以及其可能的功能仍未知晓.本文综述了环状核酸(特别是较小环的寡聚核苷酸)主要的两类合成法(酶合成法和化学合成法),并比较了它们各自的优缺点.同时阐述了各种环状功能核酸的结构特性以及它们对特定生物活性和基因功能的特异性调控,为阐明环状核酸在生物体内的产生及其作用机制的化学生物学研究提供了新的研究工具.     

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.     

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.     

CoFe2O4自形成磁性液体场致结构化对磁化的影响

The Langevin paramagnetic theory can’t describe the relation between magnetization of ferrofluids and applied magnetic field. The structuralization of ferrofluids, which is considered the main influence factor of the magnetization, is regarded. The part of magnetization works is deposited when the structure is forming. This action influences the magnetization of ferrofluids directly or indirectly. On the base of the “compressing” model, the Langevin function that usually describes the magnetization of ferrofluid is modified, and a well-fitted curve is obtained. An equation of the relation between the equivalent volume fraction after being “compressed” and the intensity of magnetic field is discovered, which approximately describes the process of magnetization. The relation between the approximate initial susceptibility and the volume fraction can be obtained from modified formula.     

Highly regioselective Buchwald–Hartwig amination at C-2 of 2,4-dichloropyridine enabling a novel approach to 2,4-bisanilinopyridine (BAPyd) libraries

The highly regioselective Buchwald–Hartwig amination at C-2 of the cheap and readily accessible reagent, 2,4-dichloropyridine with a range of anilines and heterocyclic amines is described. This new methodology is robust and provides a facile access to 4-chloro-N-phenylpyridin-2-amines on 0.25 mol scale. These intermediates undergo a further Buchwald–Hartwig amination at higher temperature to enable rapid exploration of the chemical space at C-4 and to provide a library of 2,4-bisaminopyridines.     

KMnO4-mediated oxidative CN bond cleavage of tertiary amines: Synthesis of amides and sulfonamides

KMnO₄-mediated oxidative CN bond cleavage of tertiary amines producing secondary amine was introduced, which was trapped by electrophiles (acyl chloride and sulfonyl chloride) to form amides and sulfonamides. The reaction could take place at mild condition, tolerating a wide range of function groups and affording products in moderate to excellent yields.     

Chemistry of heterocyclic compounds at the A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences, over 50 years (Review)

The review contains a concise historical account and information on the most significant researches undertaken by the staff at the A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences on the Chemistry of Heterocyclic Compounds. Dedicated to Academician of the Russian Academy of Sciences B. A. Trofimov on his 70th jubilee. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1443–1502, October, 2008.     

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.     

Sulfur-directed metal-free and regiospecific methyl C(sp3)–H imidation of thioanisoles

Regiospecific and direct imidation of the methyl C(sp³)–H bond of thioanisoles is realized under mild and metal-free conditions with N-fluorobis(benzenesulfonyl)imide as an oxidant and nitrogen source. Proposed mechanism suggests that thionium ion intermediates and a Pummerer-type reaction are involved. The imidation has advantages such as high step-economy, excellent functionality tolerance, and regiospecificity, giving structurally diverse imidation products.     

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.