核蛋白的生物功能及核肽的合成和应用

核蛋白或核肽是一类其侧链羟基通过磷酸二酯键连接到DNA 或RNA 的3′或5′端的天然生物大分子, 具有广泛的生物学效应, 包括DNA 及RNA 的复制、DNA 的转录、插入、缺失和重组等。核肽也指合成的核蛋白结合位点的片断, 作为一种新的工具既可用于研究核蛋白产生生物效应的机理, 又为开发新一类抗病毒、抗肿瘤药物开辟了道路。     

金属有机配合物对DNA的断链作用

过渡金属配合物催化DNA、RNA的断链反应研究是近年来最为活跃的前沿研究领域之一,因某些金属配合物具有核酸酶特异性催化DNA、RNA断链的功能,因而该研究对新型抗肿瘤、抗艾滋病化学药物的定向设计及其基因治疗和分子生物学研究中DNA、RNA的高度专一性定点断裂、染色体图谱分析及DNA定位诱变、基因工程中足迹技术(footprinting)以及DNA构象识别等方面均具有重要意义和应用前景,文献已报道了一些具有断裂DNA、RNA功能的金属配合物,但其中很少有含金属-碳σ键的金属有机化合物,本文首次报道了二茂铁鎓离子三氯乙酸盐和二氯二茂钛对DNA的断链作用。     

Toehold链置换辅助智能手机比色法特异性检测废水中新冠病毒靶标RNA

基于Toehold介导的链置换反应（TSDR）与DNA酶,构建了一个强特异性及低成本检测废水中SARS-CoV-2靶标RNA单碱基突变的比色生物传感器。SARS-CoV-2靶标RNA与双链DNA(dsDNA)引发TSDR,释放出完整的G-四链体序列并与氯化血红素（Hemin）结合,形成G-四链体/Hemin DNA酶,进而催化双氧水氧化3,3’,5,5’-四甲基联苯胺,使溶液呈蓝色。当SARS-CoV-2靶标RNA存在单碱基突变时,TSDR被抑制,导致裸眼观察到的溶液颜色与未突变异的靶标相比更浅。同时采用智能手机摄像头捕捉溶液的RGB值变化（ΔRGB）,对裸眼观察结果的准确性进行验证。在最优条件下,构建的比色生物传感器能够特异性识别单个碱基突变的SARS-CoV-2靶标RNA,具有用于废水中SARS-CoV-2变异毒株检测的潜力。     

双链DNA裂解-纳米金共振散射光谱探针检测痕量UO2^2＋

在pH 5.5的2-（N-吗啉）-乙磺酸缓冲液中,底物DNA和酶DNA杂交形成双链DNA（dsDNA）.当加入UO 2＋后,dsDNA中的底物DNA链被裂解,释放的裂解链DNA吸附在金纳米粒子（GN）表面,未吸附裂解链DNA的GN在NaCl存在下发生聚集,在610 nm处有一最强的共振散射峰.随着UO 2＋的浓度增大,...     

司帕沙星及均三嗪衍生物铜(II)配合物与DNA作用及其抗肿瘤活性

DNA是抗肿瘤药物的重要靶点,研究药物分子与DNA之间的作用有助于设计靶向DNA类抗肿瘤药物.合成和表征了新的三元铜（II）配合物[Cu（Sf）（PyTA）（H₂O）]·ClO₄·3.5H₂O[Sf=司帕沙星,5-氨基-1-环丙基-7-（顺-3,5-二甲基-1-哌嗪基）-6,8-二氟-1,4-二氢-4-氧-3-喹啉羧酸、PyTA=2,4-二氨基-6-（2'-吡啶基）-1,3,5-均三嗪].利用电子吸收光谱、KI荧光猝灭光谱、粘度测定以及分子对接技术研究了配合物与DNA之间作用,发现配合物以插入模式与DNA结合,结合常数K_b=1.23×10⁴ L/mol.此外,应用MTT[3-（4,5-二甲基噻唑-2）-2,5-二苯基四氮唑溴盐]比色法检测了配合物的细胞毒性作用,发现配合物对癌细胞A549、Bel-7402和Eca-109等表现出良好的抑制作用[IC₅₀=（57.0±1.6）~（77.6±1.4）μmol/L].尤为重要的是,通过单细胞凝胶电泳、Hoechst 33342染色、Annexin V-FITC/PI双染流式细胞术、测定线粒体膜电位、检测细胞色素C和胞内Ca²⁺水平及细胞周期分析探究了配合物抗肿瘤作用机制,结果表明,配合物通过DNA结合及线粒体功能障碍途径诱导细胞凋亡,使细胞S和G2/M周期发生阻滞并造成DNA损伤.     

电化学法研究苯磺酰类5-氟尿嘧啶衍生物与双链和G-四链DNA的相互作用

本文以自组装法制得的双链DNA（ds．DNA）和G-四链体DNA（G4-DNA）修饰的金电极为工作电极,以Fe（CN）63-／4-为电活性指示剂,采用循环伏安法和微分脉冲伏安法研究了非电活性苯磺酰类5-氟尿嘧啶衍生物与ds-DNA和G4．DNA的相互作用．实验结果表明：苯磺酰类5-氟尿嘧啶与ds-DNA或G4．DNA的结合常数与苯环上邻、对位取代基的得失电子能力密切相关,强吸电子基团取代有利于苯磺酰类5-氟尿嘧啶选择性结合G-四链体DNA．     

咔咯及其金属配合物与DNA的作用和抗肿瘤活性

咔咯及其金属配合物与DNA相互作用和它们的抗肿瘤活性研究已成为咔咯大环化学前沿课题之一。本文综述了咔咯及其金属配合物与DNA相互作用和关于这类化合物在抗肿瘤方面的研究进展,系统介绍了咔咯及其金属配合物与DNA结合模式、在氧化剂存在或光照条件下的核酸酶活性、与G-四链体DNA相互作用以及这类化合物抗肿瘤活性。     

氟尿嘧啶柱撑镁铝层状复合氢氧化物的结构与性能表征

氟尿嘧啶(Fluorouracil, FLU)是一种常用抗肿瘤药物,用于治疗乳腺癌、卵巢癌、胰腺癌、胃癌及头颈部癌等恶性实体瘤.氟尿嘧啶在体内转化为磷酸脱氧核糖氟尿嘧啶核苷,通过与胸苷酸合成酶复合减少DNA合成、通过伪代谢产物阻断RNA及蛋白质合成导致瘤体细胞死亡.     

β-K4H3[SiW9O37(CpTi)3]·11H2O环戊二烯钛多酸衍生物与DNA作用研究

某些过渡金属配合物具有特异性催化DNA和RNA断裂的功能, 因而研究过渡金属配合物对DNA和RNA的断链反应对新型抗肿瘤、抗艾滋病化学药物的定向设计及其基因治疗和分子生物学中DNA和RNA的高度专一性定点断裂、 DNA定位诱变和构象识别具有重要意义和应用前景[1,2]. 我们对二茂钛多酸有机金属衍生物合成及抗肿瘤活性研究表明, 环戊二烯钛多氧金属酸盐衍生物具有很高的抗肿瘤活性和较好的水溶性及稳定性, 有潜在的抗肿瘤药用价值[3].     

水溶性磷酸盐功能化的聚芴作为细胞色素c的荧光生物传感器

通过Suzuki偶联反应,在水／DMF体系下制备了一种阴离子水溶性聚芴衍生物——聚[2,7-二溴-9,9-二（6-磷酸基己基）芴-alt-苯基]钠盐（PFHPNa）．聚合物PFHPNa具有良好的水溶性和强的蓝色荧光发射．通过比较不同淬灭剂对PFHPNa和已报道的具有不同侧链长度的聚[2,7-二溴-9,9-二（6-磷酸基己基）芴-alt-苯基]钠盐（PR,PNa）的淬灭效率,研究了侧链长度对荧光传感性能的影响．对于小分子淬灭剂（甲基紫精（MV^2＋）和间5,10,15,20-四（N-甲基-4-吡啶基）卟吩（TMPyP4））而言,聚合物PFHPNa由于较长的侧链长度而表现出较低的灵敏度．     

四(3,4-二甲基苯基)卟啉钴的合成及其光学性质

采用“两步法”,以吡咯和3,4-二甲基苯甲醛为原料,合成了四(3,4-二甲基苯基)卟啉(TDMPP, 1); 1与四水醋酸钴经络合反应合成四(3,4-二甲基苯基)卟啉钴(TDMPPCo, 2),其结构经¹H NMR, IR和荧光光谱确证。考察了金属盐的预处理、反应物浓度、浓缩比和投料比对合成2的收率影响。实验结果表明：在最佳反应条件［γ=n(1)：n(四水乙酸钴)=1 ：7, c（1）为22.95 mmol·L^-1,回流（150 ℃）反应4 h,浓缩比η为75%］下,收率可达82%。     

5-羟基-3,4-二氢异喹啉-1-酮的合成

以异喹啉为起始原料,经成盐、磺化得异喹啉-5-磺酸(3),3与熔融的氢氧化钠和氢氧化钾反应得1,5-二羟基异喹啉(4),以5%Pd-C为催化剂还原4得5-羟基-3,4-二氢异喹啉-1-酮(1),总收率47.6%。1的结构经1H NMR和MS确证。     

Dynamic Ring-chain Equilibrium of Nucleophilic Thiol-yne “Click” Polyaddition for Recyclable Poly(dithioacetal)s

We report a dynamic polymerization system based on the reversible nucleophilic Michael polyaddition of activated alkynes and dithiols. Four poly(dithioacetal)s(P1-P4) were prepared via the base-catalyzed thiol-yne "click" polyaddition of two dithiols(1,4-butanedithiol(4 S) and 1,5-pentanedithiol(5 S)) and two alkynones(3-butyn-2-one(Y1) and 1-phenyl-2-propyn-1-one(Y2)) at high concentrations. We systematically investigated the base-catalyzed polymerization of 4 S and Y1(for polymer P1) under dif...     

SO2的简并四波混频光谱

简并四波混频（DegenerateFour－WaveMixingDFWM）是一项非线性光谱技术·近年来，它被成功地用于气相痕量原子、分子和自由基的探测［1，2］，而受到人们的关注．DFWM具有亚多普勒的光谱分辨、良好的时间和空间分群等特点，可以实现远距离探测，能有效地排除背景光干扰．此外，由于DFWM技术是直接用于探测体系的吸收，可以应用于无荧光或荧光量子产率低的体系和激发态具有电离和预解离等竞争通道的体系，而这两种体系用传统的激光诱导荧光（LIF）和共振多光子电离（REMPI）方法很难探测．Dreier和Rakestraw曾用DFWM技术探测火…     

Syntheses of new model compounds related to an antigenic epitope from Bupleurum falcatum L. and their distributions in various ganglioside-phospholipid monolayers

6-N-[2-(Tetradecyl)hexadecanamido]hexyl beta-D-glucopyranosyluronic acid-(1-->6)-beta-D-galactopyranosyl-(1-->6)-beta-D-galactopyranoside (1) and its clustering compound (2) carrying a tetravalent sugar unit, which are new model compounds related to a major antigenic epitope from antiulcer pectic polysaccharide of Bupleurum falcatum L., were synthesized and the distributions of 1 and 2 in mixed ganglioside (GM1, GD1a or GT1b)/phospholipid (DPPC) monolayers were observed using atomic force microscopy (AFM). AFM images showed that 1 was distributed in the GM1, GD1a and GT1b region of the mixed monolayers, in which 1 was miscible with GD1a. Specific distribution of 1 was observed in the mixed GM1/DPPC monolayer. Compound 2 was miscible with GM1, while 2 formed associations with GD1a and GT1b in the mixed monolayers. The distribution mode of 1 and 2 was different among the mixed ganglioside/DPPC monolayers.     

Inhibition effects of gangliosides G(M1), G(D1a) and G(T1b) on base-catalyzed isomerization of prostaglandin A(2)

Micellar inhibition effect of gangliosides on a degradation of drug was investigated, where ganglioside G(M1) (GM1), G(D1a) (GD1a) and G(T1b) (GTlb) whose sialic acid residue is one, two and three, respectively, were used. The base-catalyzed isomerization of prostaglandin A(2) (PGA(2)) to prostaglandin B(2) (PGB(2)) was chosen as a model experiment. The rate for the isomerization of PGA(2) was determined by measuring the concentration of PGA(2) (and PGB(2)) with a high-performance liquid chromatography. Gangliosides micelles inhibited the isomerization of PGA(2). The inhibition effect of GT1b micelles was larger than that of GD1a micelles. This result would be due to the larger absolute value of surface potential of GT1b micelles, which brings about a larger electrostatic repulsion between micellar surface and OH(-). The terminal sialic acid residue of ganglioside was effective to inhibit the isomerization of PGA(2). GM1 micelles without terminal sialic acid residue but with large aggregation number exhibited a superior steric shielding effect rather than an electrostatically repulsive effect. The inhibition effect of GM1 micelles was enhanced by the mixed micellization with the other ganglioside with a terminal sialic acid residue. GM1-GD1a or GM1-GT1b mixed micelles remarkably inhibited the isomerization of PGA(2). The physiological activity of PGs in the biological membranes containing gangliosides was also discussed.     

2-(Trimethylsilyl)ethyl glycosides. Synthesis of the asialo-GM1-tetrasaccharide, spacer glycoside, and BSA and Sepharose glycoconjugates.

The tri and tetra-saccharide glycosides beta-D-GalNAc-(1-4)-beta-D-Gal-(1-4)-beta-D-Glc-1-OTMSEt and beta-D-Gal-(1-3)-beta-D-GalNAc-(1-4)-beta-D-Gal-(1-4)-beta-D-Glc-1-OT MSEt (asialo-GM1) have been synthesized by sequential glycosylations of a suitably protected 2-(trimethylsilyl)ethyl (TMSEt) lactoside with 3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-beta-D-galactopyranosyl chloride and 2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl bromide. The tetrasaccharide glycoside was transformed into the corresponding hemiacetal sugar as well as the 1-chloro sugar. The latter was used for glycosylation of 2-bromoethanol. The resulting glycoside was used to alkylate methyl 3-mercaptopropionate and the resulting spacer glycoside was used for the preparation of the title glycoconjugates.     

Dual electron transfer pathways from 4,4'-dimethoxybenzophenone ketyl radical in the excited state to parent molecule in the ground state

Dual intermolecular electron transfer (ELT) pathways from 4,4'-dimethoxybenzophenone (1) ketyl radical (1H*) in the excited state [1H*(D1)] to the ground-state 4,4'-dimethoxybenzophenone [1(S0)] were found in 2-methyltetrahydrofuran (MTHF) by observing bis(4-methoxyphenyl)methanol cation (1H+) and 4,4'-dimethoxybenzophenone radical anion (1*-) during nanosecond-picosecond two-color two-laser flash photolysis. ELT pathway I involved the two-photon ionization of 1H* following the injection of electron to the solvent. The solvated electron was quickly trapped by 1(S0) to produce 1*-. ELT pathway II was a self-quenching-like ELT from 1H*(D1) to 1(S0) to give 1H+ and 1*-. From the fluorescence quenching of 1H*(D1), the ELT rate constant was determined to be 1.0 x 10(10) M(-1) s(-1), which is close to the diffusion-controlled rate constant of MTHF. The self-quenching-like ELT mechanism was discussed on the basis of Marcus' ELT theory.     

用循环拆分法制备手性萘乙胺

研究了1-(1-萘基)乙胺[(RS)-1]和1-(2-萘基)乙胺[(RS)-2]的循环拆分方法。以D-酒石酸为拆分剂,分别拆分(RS)-1和(RS)-2得到了(R)-1-(1-萘基)乙胺(收率31%,98%ee)和(R)-1-(2-萘基)乙胺(收率30%,98%ee),并对母液中的非目标对映异构体成功的进行了消旋化,实现了循环拆分。     

合成双酚AF的新方法

由六氟丙酮三水合物和苯胺,经缩合、重氮化、水解、Friedel-Crafts烷基化等4步反应在常压下合成了双酚 AF。首先,以五氧化二铌为催化剂,在 n (HFA•3H₂O) : n (aniline) : n (Nb₂O₅) = 2 : 1 : 0.1,回流 6 h 条件下,合成出中间体（Ⅰ）,收率高达96.3%。然后在重氮化温度为 ﹣2 ～ 2 ℃,硫酸质量分数为 14.7%,n (Ⅰ) : n (H₂SO₄) : n (NaNO₂) = 1 : 4.1 : 1.1,及水解时硫酸质量分数为 50%,n (H₂SO₄) : n (Ⅰ) = 11.0 : 1、108～112 ℃反应 1.5 ～ 2 h 的优化条件下,化合物Ⅰ经重氮化、水解后以 92.7%的高收率得到中间体 2-（4-羟基苯）六氟异丙醇（Ⅱ）;再在甲磺酸存在下,化合物Ⅱ与苯酚经Friedel-Crafts烷基化反应以 72.4% 的收率合成了目标产物双酚 AF（Ⅲ）,总收率为 64.6%（以苯胺为基准计算）。