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    • 5. 发明授权
    • Method for polynucleotide synthesis
    • 多核苷酸合成方法
    • US07417139B2
    • 2008-08-26
    • US10652054
    • 2003-08-30
    • Douglas J DellingerAgnieszka B. SierzchalaMarvin H CaruthersGeraldine F Dellinger
    • Douglas J DellingerAgnieszka B. SierzchalaMarvin H CaruthersGeraldine F Dellinger
    • C07H21/00
    • C07H21/00Y02P20/55
    • 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. In particular embodiments, the precursor has the structure: wherein: O and H represent oxygen and hydrogen, respectively R1 is hydrido, hydroxyl, protected hydroxyl, lower alkyl, modified lower alkyl, or alkoxy, one of R2 or R3 is a hydroxyl protecting group; and the other of R2 or R3 is a reactive group capable of reacting with the reactive site hydroxyl, Base is a heterocyclic base having an exocyclic amine group, and Tram is the exocyclic amine triaryl methyl protecting group.
    • 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。 在具体实施方案中,前体具有以下结构:其中:O和H分别表示氧和氢,R 1为氢,羟基,保护的羟基,低级烷基,经修饰的低级烷基或烷氧基,R2或R3中的一个为羟基保护基 ; R2或R3中的另一个是能够与反应性位点羟基反应的反应性基团,碱是具有环外胺基的杂环基,Tram是环外胺三芳基甲基保护基。
    • 6. 发明授权
    • Cleavable linker for polynucleotide synthesis
    • 用于多核苷酸合成的可切割接头
    • US07385050B2
    • 2008-06-10
    • US10652063
    • 2003-08-30
    • Douglas J DellingerGeraldine F DellingerMarvin H Caruthers
    • Douglas J DellingerGeraldine F DellingerMarvin H Caruthers
    • C07H21/00C07H19/10C07H19/20
    • C07H21/04
    • 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. In particular embodiments of methods of making the functionalized supports, a solid support, on which an available reactive group is bound, is contacted with a reagent having the structure (I) Phos-Cgp-Trl-Cgp′Nucl   (I) wherein the groups are defined as follows: Phos is a reactive phosphorus group capable of specifically reacting with an available reactive group on the support, Trl is a triaryl methyl linker group having three aryl groups, each bound to a central methyl carbon, at least one of said three aryl groups having one or more substituents, Cgp is a linking group linking the reactive phosphorus group and the triaryl methyl linker group, or is a bond linking the reactive phosphorus group and the triaryl methyl linker group, Nucl is a nucleoside moiety, wherein the nucleoside moiety is optionally part of a polynucleotide moiety, and Cgp′ is a linking group linking the nucleoside moiety and the triaryl methyl linker group, or is a bond linking the nucleoside moiety and the triaryl methyl linker group. In typical embodiments, the solid support is contacted with the reagent having the structure (I) under conditions and for a time sufficient to result in a functionalized support having a nucleoside moiety bound to the solid support via a triaryl methyl linker group.
    • 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。 在制备官能化载体的方法的具体实施方案中,在其上结合有可用的反应性基团的固体支持体与具有结构(I)的试剂接触<?in-line-formula description =“In-Line Formulas” end =“lead”?> Phos-Cgp-Trl-Cgp'Nucl(I)<?in-line-formula description =“In-line Formulas”end =“tail”?>其中定义如下:Phos 是能够与载体上可用的反应性基团特异性反应的活性磷基团,Tr1是具有三个芳基的三芳基甲基连接基团,每个芳基与中心甲基碳结合,所述三个芳基中的至少一个具有一个或多个 取代基,Cgp是连接反应性磷基团和三芳基甲基连接基团的连接基团,或者是连接反应性磷基团和三芳基甲基连接基团的键,Nuc1是核苷部分,其中核苷部分任选地是 多核苷酸部分,Cgp'是连接基团 核苷核苷部分和三芳基甲基连接基团,或是连接核苷部分和三芳基甲基连接基团的键。 在典型的实施方案中,固体支持物与具有结构(I)的试剂在足以导致具有通过三芳基甲基连接基团与固体支持物结合的核苷部分的官能化载体的条件下接触。