同构核苷类似物的合成及其性质研究
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摘要
同构核苷类似物,其光学物理性质会随着周围环境的微小变化而发生改变,被广泛应用于核酸的结构及其功能表达的研究中。运用化学合成法,设计以邻氨基苯甲酸衍生物为原料,反应得到喹唑啉衍生物碱基,此碱基与核糖反应,在醇氨溶液中水解,得到5-氯-2,4-喹唑啉二酮尿苷。并通过核磁共振波谱法、紫外可见光谱法和分子荧光光谱法确定了它的物质结构及不同极性、pH值下的紫外和荧光性质。最后通过MTT法测定5-氯-2,4-喹唑啉二酮尿苷对癌细胞增殖的影响,这为化合物在体内探针的应用提供了良好的应用前景。
Isomorphic nucleoside analogues,whose optical and physical properties change with minor changes in the surrounding environment,have been widely used in the study of nucleic acid structure and functional expression.Using the chemical synthesis method,the base of quinazoline derivative was synthesized from anthranilic acid derivatives.The base group reacted with ribose and hydrolyzed in alcohol and ammonia solution to obtain 5-chloro-2,4-quinazoline diketone uridine.The material structure and the UV and fluorescence properties at different pH values were determined by nuclear magnetic resonance spectroscopy(NMR),ultraviolet and visible spectropho tometry(UV-VIS)and molecular fluorescence spectroscopy.Finally,the effect of 5-chloro-2-azoline-4-quinazolinedione uridine on the proliferation of cancer cells was determined by MTT method,which provided a good prospect for the application of the compounds in vivo probes.
Isomorphic nucleoside analogues,whose optical and physical properties change with minor changes in the surrounding environment,have been widely used in the study of nucleic acid structure and functional expression.Using the chemical synthesis method,the base of quinazoline derivative was synthesized from anthranilic acid derivatives.The base group reacted with ribose and hydrolyzed in alcohol and ammonia solution to obtain 5-chloro-2,4-quinazoline diketone uridine.The material structure and the UV and fluorescence properties at different pH values were determined by nuclear magnetic resonance spectroscopy(NMR),ultraviolet and visible spectropho tometry(UV-VIS)and molecular fluorescence spectroscopy.Finally,the effect of 5-chloro-2-azoline-4-quinazolinedione uridine on the proliferation of cancer cells was determined by MTT method,which provided a good prospect for the application of the compounds in vivo probes.
引文
[1]Asseline U.Development and applications of fluorescent oligonucleotides[J].Curr.Org.Chem.,2006,10(4):491-518.
[2]Srivatsan S G,Famulok M.Functional nucleic acids in high throughput screening and drug Discovery[J].Comb.Chem.High Throughput Screening,2007,10(8):698-705.
[3]Shi X,Herschlag D.Fluorescence polarization anisotropy to measure RNA dynamics[J].Methods Enzymol.,2009,469:287-302.
[4]Ikeda Y,Kawahara S,Yoshinari K,et al.Specific 3′-Terminal Modification of DNA with a Novel Nucleoside Analogue that Allows a Covalent Linkage of a Nuclear Localization Signal and Enhancement of DNA Stability[J].Chembiochem,2005,6:297-303.
[5]Srivatsan S G,Tor Y.Fluorescent pyrimidine ribonucleotide:synthesis,enzymatic incorporation,and utilization[J].J.Am.Chem.Soc.,2007,129:2044-2053.
[6]李文军.新型核苷类似物的设计、合成及抗病毒活性研究[D].济南:山东大学,2012.
[7]Jordheim L P,Durantel D,Zoulim F,et al.Advances in the development of nucleoside and nucleotide analogues for cancer and viral diseases[J].Nature Reviews Drug Discovery,2013,12(6):447-464.
[8]李伟,秦汤,温新民.具有抗肿瘤活性核苷类似物研究进展[J].济宁医学院学报,2016(1):53-57.
[9]高勇.核苷类似物抗HIV的研究进展[J].国外医学(流行病学传染病学分册),2001(1):10-15.
[10]Boxall E H,Sira J,Standish R A,et al.Natural history of hepatitis B in perinatally infected carriers[J].Arch.Dis.Child.Fetal Neonatal Ed.,2004,89(5):F456-F460.
[11]张庆利,孟秀英,李晓,等.核苷类似物对肺结核合并HBV携带者的疗效观察[J].中华全科医学,2013(2):185-187.
[12]Wilson J N,Kool E T.Fluorescent DNA base replacements:reporters and sensors for biological systems[J].Org.biomol.chem.,2006,4(23):4265-4274.
[13]Yeh H C,Puleo C M,Ho Y P,et al.Tunable blinking kinetics ofcy5for precise DNA quantification and single-nucleotide difference detection[J].Biophys.J.,2008,95(2):729-737.
[14]郑洪.肿瘤细胞膜上核苷载体的荧光标记、分析及实用性研究[D].南京:东南大学,2004.
[15]李振.蛋白质与药物小分子及类似物相互作用的光谱学研究[D].郑州:郑州大学,2015.
[16]Paszyc S,Rafalska M.Photochemical properties of Yt base in aqueous solution[J].Nucleic.Acids.Res.,1979,6(1):385-397.
[17]谢晨.新型荧光核苷类似物的合成及其性质研究[D].无锡:江南大学,2016.
[18]Rist M J,Marino J P.Fluorescent nucleotide base analogs as probes of nucleic acid structure,dynamics and interactions[J].Curr.Org.Chem.,2002,6(9):775-793.
[19]Phelps K,Morris A,Beal P A.Novel modifications in RNA[J].ACS Chem.Biol.,2011,7(1):100-109.
[20]Hall K B.2-Aminopurine as a probe of RNA conformational transitions[J].Methods Enzymol.,2009,469:269-285.
[21]Xie Y,Dix A V,Tor Y.Antibiotic selectivity for prokaryotic vs.eukaryotic decoding sites[J].Chemical Communications,2010,46(30):5542-5544.
[22]Xie Y,Maxson T,Tor Y.Fluorescent ribonucleoside as a FRET acceptor for tryptophan in native proteins[J].Journal of the American Chemical Society,2010,132(34):11896-11897.
[23]Ward D C,Reich E,Stryer L.Fluorescence studies of nucleotides and polynucleotides I.Formycin,2-aminopurine riboside,2,6-diaminopurine riboside,and their derivatives[J].Journal of Biological Chemistry,1969,244(5):1228-1237.
[24]Sinkeldam R W,Greco N J,Tor Y.Fluorescent analogs of biomolecular building blocks:design,properties,and applications[J].Chemical reviews,2010,110(5):2579-2619.
[25]Hall K B.2-Aminopurine as a probe of RNA conformational transitions[J].Methods in enzymology,2009,469:269-285.
[2]Srivatsan S G,Famulok M.Functional nucleic acids in high throughput screening and drug Discovery[J].Comb.Chem.High Throughput Screening,2007,10(8):698-705.
[3]Shi X,Herschlag D.Fluorescence polarization anisotropy to measure RNA dynamics[J].Methods Enzymol.,2009,469:287-302.
[4]Ikeda Y,Kawahara S,Yoshinari K,et al.Specific 3′-Terminal Modification of DNA with a Novel Nucleoside Analogue that Allows a Covalent Linkage of a Nuclear Localization Signal and Enhancement of DNA Stability[J].Chembiochem,2005,6:297-303.
[5]Srivatsan S G,Tor Y.Fluorescent pyrimidine ribonucleotide:synthesis,enzymatic incorporation,and utilization[J].J.Am.Chem.Soc.,2007,129:2044-2053.
[6]李文军.新型核苷类似物的设计、合成及抗病毒活性研究[D].济南:山东大学,2012.
[7]Jordheim L P,Durantel D,Zoulim F,et al.Advances in the development of nucleoside and nucleotide analogues for cancer and viral diseases[J].Nature Reviews Drug Discovery,2013,12(6):447-464.
[8]李伟,秦汤,温新民.具有抗肿瘤活性核苷类似物研究进展[J].济宁医学院学报,2016(1):53-57.
[9]高勇.核苷类似物抗HIV的研究进展[J].国外医学(流行病学传染病学分册),2001(1):10-15.
[10]Boxall E H,Sira J,Standish R A,et al.Natural history of hepatitis B in perinatally infected carriers[J].Arch.Dis.Child.Fetal Neonatal Ed.,2004,89(5):F456-F460.
[11]张庆利,孟秀英,李晓,等.核苷类似物对肺结核合并HBV携带者的疗效观察[J].中华全科医学,2013(2):185-187.
[12]Wilson J N,Kool E T.Fluorescent DNA base replacements:reporters and sensors for biological systems[J].Org.biomol.chem.,2006,4(23):4265-4274.
[13]Yeh H C,Puleo C M,Ho Y P,et al.Tunable blinking kinetics ofcy5for precise DNA quantification and single-nucleotide difference detection[J].Biophys.J.,2008,95(2):729-737.
[14]郑洪.肿瘤细胞膜上核苷载体的荧光标记、分析及实用性研究[D].南京:东南大学,2004.
[15]李振.蛋白质与药物小分子及类似物相互作用的光谱学研究[D].郑州:郑州大学,2015.
[16]Paszyc S,Rafalska M.Photochemical properties of Yt base in aqueous solution[J].Nucleic.Acids.Res.,1979,6(1):385-397.
[17]谢晨.新型荧光核苷类似物的合成及其性质研究[D].无锡:江南大学,2016.
[18]Rist M J,Marino J P.Fluorescent nucleotide base analogs as probes of nucleic acid structure,dynamics and interactions[J].Curr.Org.Chem.,2002,6(9):775-793.
[19]Phelps K,Morris A,Beal P A.Novel modifications in RNA[J].ACS Chem.Biol.,2011,7(1):100-109.
[20]Hall K B.2-Aminopurine as a probe of RNA conformational transitions[J].Methods Enzymol.,2009,469:269-285.
[21]Xie Y,Dix A V,Tor Y.Antibiotic selectivity for prokaryotic vs.eukaryotic decoding sites[J].Chemical Communications,2010,46(30):5542-5544.
[22]Xie Y,Maxson T,Tor Y.Fluorescent ribonucleoside as a FRET acceptor for tryptophan in native proteins[J].Journal of the American Chemical Society,2010,132(34):11896-11897.
[23]Ward D C,Reich E,Stryer L.Fluorescence studies of nucleotides and polynucleotides I.Formycin,2-aminopurine riboside,2,6-diaminopurine riboside,and their derivatives[J].Journal of Biological Chemistry,1969,244(5):1228-1237.
[24]Sinkeldam R W,Greco N J,Tor Y.Fluorescent analogs of biomolecular building blocks:design,properties,and applications[J].Chemical reviews,2010,110(5):2579-2619.
[25]Hall K B.2-Aminopurine as a probe of RNA conformational transitions[J].Methods in enzymology,2009,469:269-285.