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核苷

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Intracellularly, didanosine is converted by cellular enzymes to the active metabolite, dideoxyadenosine 5'-triphosphate.

去羟肌苷是天然核苷—去氧腺苷3-羟基被氢取代的合成的核苷类似物。

After nucleosides were extracted from urine on phenyl boronic acid affinity chromatography, the analysis was performed on a column (46 mm id×250 mm, 5 μm) at 22 ℃ using a linear gradient elution comprising 25 mmol/L KH2PO4 solution (pH 455) and 60% methanol in water with UV detection at 260 nm.

用该法测定了41例肠癌患者和52例正常人尿中15种核苷的含量(用核苷与肌酐的摩尔比表示,下同),结果表明肠癌患者中有12种核苷的含量比正常人显著性增高(P 001)。以15种核苷的含量作为参量,结合主成分分析区分正常人和肠癌患者,对癌症病人的识别率达76%(31/41)。

These compounds were identified as follows:chrysophanol (FP-1),physcion(FP-2),eriosematin(FP-3),scoparone(FP-4),lupeol(FP-5),betulinic acid(FP-6),3\',4\'-Dihydroxy-trans-cinamic acid octacosyl ester(FP-7),β-sitosterol (FP-8),flemiphilippinone A(FP-9),monopalmitin(FP-10),emodin(FP-11),islandicin (FP-12),salicylic acid(FP-13),p-methoxyphenylpropionic acid(FP-14),trideca-1, 3-diene(FP-15),lupinifolin(FP-16),flemichin D(FP-17),flemiphilippinin A(FP-18), auriculasin(FP-19),erythrinin B(FP-20),6-C-prenylluteolin(FP-21), 8-(1,1-dimethylallyl) genistein(FP-22),flemiphilippinin E(FP-23),flemiphilippinin F (FP-24),5,7,3\',4\'-tetrahydroxy-6,8-diprenylisoflavone(FP-25),flemiphilippinin D (FP-26),dorsmaninsⅠ(FP-27),osajin(FP-28),6,8-diprenyleriodictyol(FP-29), lupinalbin A(FP-30),genistein(FP-31),3\'-O-methylorobol(FP-32),orobol(FP-33), 5,7,2\',3\',4\'-pentahrdroxyflavone(FP-34),the mixture of biochanin A and prunetin (FP-35 and 36),genistin(FP-37),sophororicoside(FP-38),3\'-O-methylorobol-7-glucoside(FP-39),the mixture of sissotrin and prunetin 4\'-O-β-D-glucoside(FP-40 and 41),adenosine(FP-42) and luteoloside(FP-43,mixture).

这些化合物分别为大黄酚(FP-1)、大黄素甲醚(FP-2)、eriosematin(FP-3)、滨蒿内酯(FP-4)、羽扇豆醇(FP-5)、白桦酸(FP-6)、咖啡酸二十八烷酯(FP-7)、β-谷甾醇(FP-8)、蔓性千斤拔酮A(FP-9)、单棕榈酸甘油酯(FP-10)、大黄素(FP-11)、islandicin(FP-12)、水杨酸(FP-13)、对甲氧基苯丙酸(FP-14)、十三烷-1,4-二烯烃(FP-15)、lupinifolin(FP-16)、千斤拔素D(FP-17)、蔓性千斤拔素A(FP-18)、auriculasin(FP-19)、erythrinin B(FP-20)、6-C-异戊烯基木犀草素(FP-21)、8-(1,1-二甲烯丙基)-染料木黄酮(FP-22)、蔓性千斤拔素E(FP-23)、蔓性千斤拔素F(FP-24)、5,7,3′,4′-四羟基-6,8-双异戊烯基异黄酮(FP-25)、蔓性千斤拔素D(FP-26)、dorsmaninsⅠ(FP-27)、osajin(FP-28)、6,8-双异戊烯基圣草素(FP-29)、lupinalbin A(FP-30)、染料木黄酮(FP-31)、3\'-O-甲基香豌豆苷元(FP-32)、奥洛醇(FP-33)、5,7,2′,3′,4′-五羟基黄酮(FP-34)、鹰嘴豆素甲和樱黄素的混合物(FP-35和FP-36)、染料木苷(FP-37)、槐属苷(FP-38)、7-葡萄糖基-3\'-O-甲基香豌豆苷(FP-39)、印度黄檀苷和樱黄素4′-O-β-D-葡萄糖苷的混合物(FP-40和FP-41)、腺嘌呤核苷(FP-42)和木犀草苷(FP-43,混合物)。

Glioma is still one of refractory disease in the neurosurgical field; the development of new primary and adjuvant treatment is vital. Recently, the gene therapy of glioma is developed rapidly and there are many methods about the gene therapy that include: suicide gene therapy, immunologic gene therapy, drug resistangce gene therapy, angiostatin gene therapy and so on. The sucide gene therapy is the most potential approach of antitumer, these nonmammalian genes encode enzyme that convert nontoxic prodrugs into highly toxic metablites. Cells transfected with suicide genes are targeted for specific negative selection, witch can be induced by administrtion of the corresponding produg. Among the enzyme/produg combinations, two of the best characterized system are herpes simplex virus thymidine kinase /ganciclovir and Escherichia coli cytosine deaminase /5-flourocytosine (5-FC). The formor can convert the antiviral nucleoside analogs acyclovir , ganciclovir to their nucleoside monophosphate derivatives, the monophosphate forms are subsequently phosphorylated by endogenus cellular kinases to triphosphates, these molecules are potent inhibitors of DNA synthesis.

近年来脑胶质瘤的基因治疗发展迅速,应运而生的方法有自杀基因、免疫基因、多药耐药基因以及抗血管生成基因等,其中自杀基因被认为是最有前景的基因治疗方法,它又称病毒介导的酶/药物前体疗法,是利用转基因技术将哺乳动物细胞中所不含有的自杀基因转入到哺乳动物肿瘤细胞中,该基因表达的产物可将无毒的药物前体转化为毒性药物,从而选择性杀伤该肿瘤细胞,常用的自杀基因有单纯疱疹病毒-胸苷激酶基因和大肠杆菌胞嘧啶脱氨酶基因,前者催化无毒性抗病毒核苷类似物如丙氧鸟苷、无环鸟苷等成为单磷酸核苷衍生物,然后在内源性细胞激酶作用下转化为具有明显毒性的三磷酸核苷,作为DNA合成链的终止剂和DNA合成酶的抑制剂,干扰细胞DNA的合成;后者编码的胞嘧啶脱氨酶可催化5-氟胞嘧啶(5-FC)脱氨成为5-氟尿嘧啶(5-FU),然后代谢为有毒性的5-氟尿嘧啶-5′三磷酸(5-FUTP)和5-氟-2′脱氧尿嘧啶-5′磷酸(5-FdUTP),5-FUTP通过与UTP竞争性结合而抑制mRNA和tRNA的合成,5-FdUTP则作用于胸苷合成酶,导致TMP衰竭而阻止DNA的合成,最终诱导肿瘤细胞凋亡。

They were two new compounds, [cyclo(Pro-Val-Phe-Phe-Pro-Val-Phe-Ser-Leu),7],[2-N-(1-methoxycarbonylethyl)guanosine, 10], and eight known compounds,(p-hydroxybenzoic acid, 1),(methyl succinate, 2),(russulaceramide, 3),(phenylalanine, 4),(guanine, 5),(β-carboline, 6),(uridine, 8), and (adenosine, 9). All the compounds were isolated from Amanita exitialis for the first time.

分别为:对羟基苯甲酸(p-hydroxybenzoic acid,1)、丁二酸二甲酯(methyl succinate,2)、神经酰胺(russulaceramide,3)、苯丙氨酸(phenylalanine,4)、鸟嘌呤核苷(guanine,5)、β-咔啉(β-carboline,6)、环(脯氨酸-缬氨酸-苯丙氨酸-苯丙氨酸-脯氨酸-缬氨酸-苯丙氨酸-丝氨酸-亮氨酸) [cyclo(Pro-Val-Phe-Phe-Pro-Val-Phe-Ser-Leu),7]、尿嘧啶核苷(uridine,8)、腺嘌呤核苷(adenosine,9)、2-N-(1-甲氧羰基乙基)鸟苷[2-N-(1-Methoxycarbonylethyl)guanosine, 10]。10个化合物均为首次从致命鹅膏中分离得到,其中化合物7和10为新化合物。

In Cordyceps sinensis.,the totle contents of adenosine、hypoxanthosine、guanosine and uridine were more than 2.50mg/g, and the content of adenosine were more than 0.75mg/g.

结果:1。建立了冬虫夏草中核苷及其核苷碱基的HPLC测定分析方法,测定了冬虫夏草与其混淆品及伪品中5个核苷类成分的含量。

The nucleosides and their bases in Cordyceps sinensis. of different origin and in its adulterations and counterfeits were studied by HPLC. The components and contents of nucleosides and their bases in Cordyceps sinensis.,and in the adulterants and the counterfeits were compared to find the difference among them.

采用HPLC法对不同产地的冬虫夏草中核苷及其核苷碱基进行测定研究,并用该方法测定混淆品及伪品中核苷核苷碱基的含量,比较正品、混淆品及伪品中核苷核苷碱基的种类和含量,找出它们之间的差异规律。

HPLC method can determine the contents of the nucleosides and their bases in the Cordyceps sinensis. and in its adulterants and counterfeits. The results showed that the totle contents of uridine, hypoxanthosine, guanosine, adenosine, and the content of adenosine can be used as a effective method for quality assess of Cordyceps sinensis .and distinguishing its counterfeits and adulterations.

本课题建立了HPLC法检测冬虫夏草及其混淆品与伪品中核苷核苷碱基含量的方法,可为冬虫夏草内在质量评定提供参考依据,并为冬虫夏草及其混淆品与伪品的区分提供一种判定依据,即可根据主成分I 、II、III、V四个核苷的总含量及V的含量作为区分冬虫夏草与混淆品及伪品的指标。

HPLC/MS/ MS was used to analyse the nucleosides in Cordyceps sinensis .and its counterfeits and adulterations. Compared the samples with the standard samples,the result showed that the main fragment chromatogram were similar.The four nucleosides in Cordyceps sinensis .and its counterfeits and adulterations were identified by MS/ MS.The totle content of uridine、hypoxanthosine、guanosine、adenosine in Cordyceps sinensis .was from 2.473 mg/g to2.830 mg/g ,the content of adenosine was from 0.850 mg/g to1.009 mg/g .

应用HPLC-MS对冬虫夏草及其混淆品与伪品中的四个核苷成分进行二级质谱定性分析,并与对照品进行比较,结果显示,冬虫夏草及其混淆品与伪品均能产生与相应对照品一致的主要碎片离子峰,进一步说明,冬虫夏草及其混淆品与伪品中均含有尿苷、肌苷、鸟苷及腺苷四种核苷成分。

After overcoming the flux shift during the process, the production ability of strains could be the limiting factor for further increasing the production. To avoid the random modification on strains, the comprehensive enzymatic study of nucleoside producing-pathway was conducted on four strains with different producing ability. And the results could be used to direct further reconstruction of strains. It was also found that nucleotidase was of much importance to nucleoside production.

在成功克服了代谢流的迁移之后,菌株的代谢能力可能成为了进一步提高产率的限制因素,为了避免对生产菌的进一步改造中的盲目性,对四株不同菌株间嘌呤途径关键酶活力的系统测定,对肌苷、鸟苷生产菌种的酶学特征有了全面的了解;并发现了核苷降解酶对于核苷生产能力至关重要;酶学特性研究对肌苷、鸟苷生产菌的进一步改造提供了方向。

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