Systematic evolution of ligands by exponential enrichment: blended SELEX
    6.
    发明授权
    Systematic evolution of ligands by exponential enrichment: blended SELEX 失效
    配体通过指数富集系统演化:混合SELEX

    公开(公告)号:US07176295B2

    公开(公告)日:2007-02-13

    申请号:US10263456

    申请日:2002-10-02

    摘要: A method is described for generating blended nucleic acid ligands containing non-nucleic acid functional units. Specifically, a SELEX identified RNA ligand to the integrin gpIIbIIIa is conjugated to the peptide Gly-Arg-Gly-Asp-Thr-Pro (SEQ ID NO:1). This blended RNA ligand inhibits the biological activity of gpIIbIIIa with high specificity. Also described is a single-stranded DNA ligand to elastase coupled to N-methoxysuccinyl-Ala-Ala-Pro-Val-chloromethyl ketone (SEQ ID NO:2). This elastase blended nucleic acid ligand inhibits the biological activity of elastase.

    摘要翻译: 描述了一种用于产生含有非核酸功能单元的混合核酸配体的方法。 具体地,将SELEX鉴定的整合素gpIIbIIIa的RNA配体与肽Gly-Arg-Gly-Asp-Thr-Pro(SEQ ID NO:1)缀合。 这种混合RNA配体以高特异性抑制gpIIbIIIa的生物活性。 还描述了与N-甲氧基琥珀酰基-Ala-Ala-Pro-Val-氯甲基酮(SEQ ID NO:2)偶联的弹性蛋白酶的单链DNA配体。 该弹性蛋白酶共混核酸配体抑制弹性蛋白酶的生物活性。

    Pyrimidine nucleosides as therapeutic and diagnostic agents
    7.
    发明授权
    Pyrimidine nucleosides as therapeutic and diagnostic agents 失效
    嘧啶核苷作为治疗和诊断剂

    公开(公告)号:US5959100A

    公开(公告)日:1999-09-28

    申请号:US622772

    申请日:1996-03-27

    CPC分类号: C07H11/02 C07H19/06 C07H19/16

    摘要: Modified nucleosides and methods of making and using the nucleosides are disclosed. The compounds can be prepared by reacting nucleoside starting materials that contain a suitable leaving group at one or more of the carbon atoms in the purine or pyrimidine ring, with a vinylstannane, carbon monoxide, and a palladium catalyst to provide 1-ene-3-one intermediates. These intermediates are then reacted with suitably functionalized primary or secondary amines via a Michael reaction. When the intermediate is a 5-position modified pyrimidine ring, and the amine contains a second hydrogen, it can do a second Michael reaction with the ene-one or the ene-imine in the pyrimidine ring. Appropriate modification of the amine reactant can yield products with various bioactivities. The nucleosides can be used therapeutically as anti-cancer, anti-bacterial or anti-viral drugs. The nucleosides can also be used for diagnostic applications, for example, by incorporating a radiolabel or fluorescent label into the molecule. The nucleosides can be used to prepare oligonucleotides for use in various applications, either alone or in combination with other modified nucleosides and/or naturally occurring nucleosides.

    摘要翻译: 公开了修饰的核苷和制备和使用核苷的方法。 可以通过使含有嘌呤或嘧啶环中的一个或多个碳原子上的合适的离去基团的核苷起始原料与乙烯基苯烷,一氧化碳和钯催化剂反应来制备化合物,以提供1-烯-3-醇, 一个中间体。 然后通过迈克尔反应将这些中间体与适当官能化的伯胺或仲胺反应。 当中间体是5-位修饰的嘧啶环,并且胺含有第二个氢时,它可以与嘧啶环中的一个或烯 - 亚胺进行第二个迈克尔反应。 胺反应物的适当改性可产生具有各种生物活性的产物。 核苷可以用作治疗性的抗癌,抗细菌或抗病毒药物。 核苷也可用于诊断应用,例如通过在分子中掺入放射性标记或荧光标记。 核苷可用于制备用于各种应用的寡核苷酸,单独使用或与其它修饰的核苷和/或天然存在的核苷组合。

    Urea nucleosides as therapeutic and diagnostic agents
    9.
    发明授权
    Urea nucleosides as therapeutic and diagnostic agents 有权
    尿素核苷作为治疗和诊断剂

    公开(公告)号:US06441161B1

    公开(公告)日:2002-08-27

    申请号:US09707253

    申请日:2000-11-06

    IPC分类号: C07H1900

    CPC分类号: C07H11/02 C07H19/06 C07H19/16

    摘要: Modified nucleosides and methods of making and using the nucleosides are disclosed. The compounds can be prepared by reacting nucleoside starting materials that contain a suitable leaving group at one or more of the carbon atoms in the purine or pyrimidine ring, with a vinylstannane, carbon monoxide, and a palladium catalyst to provide 1-ene-3-one intermediates. These intermediates are then reacted with suitably functionalized primary or secondary amines via a Michael reaction. When the intermediate is a 5-position modified pyrimidine ring, and the amine contains a second hydrogen, it can do a second Michael reaction with the ene-one or the ene-imine in the pyrimidine ring. Appropriate modification of the amine reactant can yield products with various bioactivities. The nucleosides can be used therapeutically as anti-cancer, anti-bacterial or anti-viral drugs. The nucleosides can also be used for diagnostic applications, for example, by incorporating a radiolabel or fluorescent label into the molecule. The nucleosides can be used to prepare oligonucleotides for use in various applications, either alone or in combination with other modified nucleosides and/or naturally occurring nucleosides.

    摘要翻译: 公开了修饰的核苷和制备和使用核苷的方法。 可以通过使含有嘌呤或嘧啶环中的一个或多个碳原子上的合适的离去基团的核苷起始原料与乙烯基苯烷,一氧化碳和钯催化剂反应来制备化合物,以提供1-烯-3-醇, 一个中间体。 然后通过迈克尔反应将这些中间体与适当官能化的伯胺或仲胺反应。 当中间体是5-位修饰的嘧啶环,并且胺含有第二个氢时,它可以与嘧啶环中的一个或烯 - 亚胺进行第二个迈克尔反应。 胺反应物的适当改性可产生具有各种生物活性的产物。 核苷可以用作治疗性的抗癌,抗细菌或抗病毒药物。 核苷也可用于诊断应用,例如通过在分子中掺入放射性标记或荧光标记。 核苷可用于制备用于各种应用的寡核苷酸,单独使用或与其它修饰的核苷和/或天然存在的核苷组合。