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    Methods of synthesizing oligonucleotides using carbonate protecting groups and alpha-effect nucleophile deprotection
    1.
    发明申请
    Methods of synthesizing oligonucleotides using carbonate protecting groups and alpha-effect nucleophile deprotection 有权
    使用碳酸酯保护基和α-效应亲核体脱保护合成寡核苷酸的方法

    公开(公告)号：US20080076913A1

    公开(公告)日：2008-03-27

    申请号：US11899828

    申请日：2007-09-06

    申请人： Douglas Dellinger ,  Marvin Caruthers ,  Jason Betley

    发明人： Douglas Dellinger ,  Marvin Caruthers ,  Jason Betley

    IPC分类号： C07H21/00

    CPC分类号： C07H19/10 ,  C07B2200/11 ,  C07H19/20 ,  C07H21/00 ,  C07H21/04 ,  C40B40/06 ,  C40B50/14 ,  Y02P20/55

    摘要： The invention provides methods for synthesizing oligonucleotides using nucleoside monomers having carbonate protected hydroxyl groups that are deprotected with α-effect nucleophiles. The α-effect nucleophile irreversibly cleave the carbonate protecting groups while simultaneously oxidizing the internucleotide phosphite triester linkage to a phosphodiester linkage. The procedure may be carried out in aqueous solution at neutral to mildly basic pH. The method eliminates the need for separate deprotection and oxidation steps, and, since the use of acid to remove protecting groups is unnecessary, acid-induced depurination is avoided. Fluorescent or other readily detectable carbonate protecting groups can be used, enabling monitoring of individual reaction steps during oligonucleotide synthesis. The invention is particularly useful in the highly parallel, microscale synthesis of oligonucleotides.

    摘要翻译： 本发明提供了使用具有碳酸酯保护的羟基的核苷单体合成寡核苷酸的方法，所述羟基被α-效应亲核试剂去保护。 α-效应亲核试剂不可逆地切割碳酸酯保护基团，同时将磷酸核苷酸亚磷酸三酯键与磷酸二酯键连接。 该方法可以在中性至弱碱性pH的水溶液中进行。 该方法不需要单独的脱保护和氧化步骤，并且由于不需要使用酸去除保护基团，所以避免了酸诱导的去血。 可以使用荧光或其它容易检测的碳酸酯保护基团，使得能够监测寡核苷酸合成期间的各个反应步骤。 本发明在寡核苷酸的高度平行，微尺度合成中特别有用。

    Methods of synthesizing oligonucleotides using carbonate protecting groups and alpha-effect nucleophile deprotection
    2.
    发明申请
    Methods of synthesizing oligonucleotides using carbonate protecting groups and alpha-effect nucleophile deprotection 有权
    使用碳酸酯保护基和α-效应亲核体脱保护合成寡核苷酸的方法

    公开(公告)号：US20060252924A1

    公开(公告)日：2006-11-09

    申请号：US11453734

    申请日：2006-06-15

    申请人： Douglas Dellinger ,  Marvin Caruthers ,  Jason Betley

    发明人： Douglas Dellinger ,  Marvin Caruthers ,  Jason Betley

    IPC分类号： C07H21/04

    CPC分类号： C07H19/10 ,  C07B2200/11 ,  C07H19/20 ,  C07H21/00 ,  C07H21/04 ,  C40B40/06 ,  C40B50/14 ,  Y02P20/55

    摘要： The invention provides methods for synthesizing oligonucleotides using nucleoside monomers having carbonate protected hydroxyl groups that are deprotected with α-effect nucleophiles. The α-effect nucleophile irreversibly cleave the carbonate protecting groups while simultaneously oxidizing the internucleotide phosphite triester linkage to a phosphodiester linkage. The procedure may be carried out in aqueous solution at neutral to mildly basic pH. The method eliminates the need for separate deprotection and oxidation steps, and, since the use of acid to remove protecting groups is unnecessary, acid-induced depurination is avoided. Fluorescent or other readily detectable carbonate protecting groups can be used, enabling monitoring of individual reaction steps during oligonucleotide synthesis. The invention is particularly useful in the highly parallel, microscale synthesis of oligonucleotides.

    摘要翻译： 本发明提供了使用具有碳酸酯保护的羟基的核苷单体合成寡核苷酸的方法，所述羟基被α-效应亲核试剂去保护。 α-效应亲核试剂不可逆地切割碳酸酯保护基团，同时将磷酸核苷酸亚磷酸三酯键与磷酸二酯键连接。 该方法可以在中性至弱碱性pH的水溶液中进行。 该方法不需要单独的脱保护和氧化步骤，并且由于不需要使用酸去除保护基团，所以避免了酸诱导的去血。 可以使用荧光或其它容易检测的碳酸酯保护基团，使得能够监测寡核苷酸合成期间的各个反应步骤。 本发明在寡核苷酸的高度平行，微尺度合成中特别有用。

    Cleavable linker for polynucleotide synthesis
    6.
    发明申请
    Cleavable linker for polynucleotide synthesis 有权
    用于多核苷酸合成的可切割接头

    公开(公告)号：US20050048497A1

    公开(公告)日：2005-03-03

    申请号：US10652063

    申请日：2003-08-30

    申请人： Douglas Dellinger ,  Geraldine Dellinger ,  Marvin Caruthers

    发明人： Douglas Dellinger ,  Geraldine Dellinger ,  Marvin Caruthers

    IPC分类号： C07H21/04 ,  C12Q1/68

    CPC分类号： C07H21/04

    摘要： Functionalized supports for polynucleotide synthesis are disclosed. The supports have linker moieties that are stable to conditions used in polynucleotide synthesis, but may be cleaved to release synthesized polynucleotides from the support. Methods of making the functionalized supports and methods of using are also disclosed.

    摘要翻译： 公开了用于多核苷酸合成的官能化载体。 载体具有对于多核苷酸合成中使用的条件稳定的接头部分，但可被切割以从载体释放合成的多核苷酸。 还公开了制备官能化载体的方法和使用方法。

    Method for polynucleotide synthesis
    8.
    发明申请
    Method for polynucleotide synthesis 失效
    多核苷酸合成方法

    公开(公告)号：US20050048601A1

    公开(公告)日：2005-03-03

    申请号：US10652054

    申请日：2003-08-30

    申请人： Douglas Dellinger ,  Geraldine Dellinger ,  Agnieszka Sierzchala ,  Marvin Caruthers

    发明人： Douglas Dellinger ,  Geraldine Dellinger ,  Agnieszka Sierzchala ,  Marvin Caruthers

    IPC分类号： C07H21/00 ,  C07K1/02 ,  C08G63/48 ,  C12P21/06

    CPC分类号： C07H21/00 ,  Y02P20/55

    摘要： Methods of forming an internucleotide bond are disclosed. Such methods find use in synthesis of polynucleotides. The method involves contacting a functionalized support with a precursor having an exocyclic amine triaryl methyl protecting group under conditions and for a time sufficient to result in internucleotide bond formation. The functionalized support includes a solid support, a triaryl methyl linker group, and a nucleoside moiety having a reactive site hydroxyl, the nucleoside moiety attached to the solid support via the triaryl methyl linker group.

    摘要翻译： 公开了形成核苷酸间键的方法。 这些方法可用于多核苷酸的合成。 该方法包括使官能化的载体与具有环外胺三芳基甲基保护基团的前体在足以导致形成核苷酸键的条件下进行接触。 官能化载体包括固体支持物，三芳基甲基连接基团和具有反应性位点羟基的核苷部分，所述核苷部分通过三芳基甲基连接基团连接到固体支持物上。