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1. 发明授权

US6087491A Extremely high purity oligonucleotides and methods of synthesizing them using dimer blocks 失效
标题翻译：极高纯度的寡核苷酸和使用二聚体嵌段合成它们的方法
公开(公告)号：US6087491A
公开(公告)日：2000-07-11
申请号：US827561
申请日：1997-05-02
申请人： Jin-Yan Tang , Nandkumar Bongle , Jose Gonzalez , Warren E. Schwartz
发明人： Jin-Yan Tang , Nandkumar Bongle , Jose Gonzalez , Warren E. Schwartz
IPC分类号： C07H21/00
CPC分类号： C07H21/00
摘要： The present invention comprises an improved method of synthesizing oligonucleotides. The method comprises employing dinucleotides (or "dimer blocks") as the basic synthetic unit building block. The method results in extremely high purity oligonucleotides in which the N-1 content is very low, generally less than 1-2% of the full length, N, oligonucleotide. We have found that synthesis using dinucleotide phosphorothioates results in oligonucleotides having very little phosphodiester content. Furthermore, we have found that the amount of dimer required in each coupling step can be less than about 6 and is preferably about 2 equivalents. Synthesis of oligonucleotides according to the dimer block approach described herein can also be conducted without the capping step that has heretofore been deemed necessary after each coupling.
摘要翻译：本发明包括一种合成寡核苷酸的改进方法。该方法包括使用二核苷酸（或“二聚体嵌段”）作为基本合成单元结构单元。该方法产生非常高纯度的寡核苷酸，其中N-1含量非常低，通常小于全长N，寡核苷酸的1-2％。我们已经发现，使用二核苷酸硫代磷酸酯的合成导致寡核苷酸具有非常少的磷酸二酯含量。此外，我们已经发现，每个偶联步骤中所需的二聚体的量可以小于约6，优选约为2当量。根据本文所述的二聚体嵌段方法的寡核苷酸的合成也可以在每次偶联之前已经被认为是必要的封端步骤的情况下进行。

2. 发明授权

US06310198B1 Extremely high purity oligonucleotides and methods of synthesizing them using dimer blocks 失效
标题翻译：极高纯度的寡核苷酸和使用二聚体嵌段合成它们的方法
公开(公告)号：US06310198B1
公开(公告)日：2001-10-30
申请号：US09545273
申请日：2000-04-07
申请人： Jin-Yan Tang , Nandkumar Bongle , Jose Gonzalez , Warren E. Schwartz
发明人： Jin-Yan Tang , Nandkumar Bongle , Jose Gonzalez , Warren E. Schwartz
IPC分类号： C07H2100
CPC分类号： C07H21/00
摘要： The present invention comprises an improved method of synthesizing oligonucleotides. The method comprises employing dinucleotides (or “dimer blocks”) as the basic synthetic unit building block. The method results in extremely high purity oligonucleotides in which the N−1 content is very low, generally less than 1-2% of the full length, N, oligonucleotide. We have found that synthesis using dinucleotide phosphorothioates results in oligonucleotides having very little phosphodiester content. Furthermore, we have found that the amount of dimer required in each coupling step can be less than about 6 and is preferably about 2 equivalents. Synthesis of oligonucleotides according to the dimer block approach described herein can also be conducted without the capping step that has heretofore been deemed necessary after each coupling.
摘要翻译：本发明包括一种合成寡核苷酸的改进方法。该方法包括使用二核苷酸（或“二聚体嵌段”）作为基本合成单元结构单元。该方法产生非常高纯度的寡核苷酸，其中N-1含量非常低，通常小于全长N，寡核苷酸的1-2％。我们已经发现，使用二核苷酸硫代磷酸酯的合成导致寡核苷酸具有非常少的磷酸二酯含量。此外，我们已经发现，每个偶联步骤中所需的二聚体的量可以小于约6，优选约为2当量。根据本文所述的二聚体嵌段方法的寡核苷酸的合成也可以在没有在每次偶联之后被认为是必要的封端步骤的情况下进行。

3. 发明授权

US5668268A Passivated polymer supports for nucleic acid synthesis 失效
标题翻译：用于核酸合成的钝化聚合物载体
公开(公告)号：US5668268A
公开(公告)日：1997-09-16
申请号：US562841
申请日：1995-11-27
申请人： Jin-Yan Tang , Jimmy X. Tang
发明人： Jin-Yan Tang , Jimmy X. Tang
IPC分类号： C07H21/00 , C07H21/04 , C12Q1/68
CPC分类号： C07H21/00
摘要： The invention provides passivated organic polymer supports, processes for their preparation and processes for their use in oligonucleotide synthesis that allow for highly efficient solid phase synthesis of oligonucleotides.
摘要翻译：本发明提供钝化的有机聚合物载体，其制备方法及其用于寡核苷酸合成中的方法，其允许寡核苷酸的高效固相合成。

4. 发明授权

US06500944B2 Sulfurizing reagent: 3-aryl-1,2,4-dithiazoline-5-ones 失效
标题翻译：硫化试剂：3-芳基-1,2,4-二噻唑啉-5-酮
公开(公告)号：US06500944B2
公开(公告)日：2002-12-31
申请号：US08895136
申请日：1997-07-16
申请人： Saroj K. Roy , Jin-Yan Tang
发明人： Saroj K. Roy , Jin-Yan Tang
IPC分类号： C07H2100
CPC分类号： C07D285/01 , C07H21/00
摘要： The invention relates to the chemical synthesis of oligonucleotides and to chemical entities useful in such synthesis. More particularly, the invention relates to sulfurization of the internucleotide linkages of oligonucleotides. The invention provides a process to synthesize new sulfur transfer reagents and a process for their use in sulfurizing oligonucleotides. The sulfur transfer reagents according to the invention are inexpensive to make, stable in storage and in solution, and highly efficient in sulfurization.
摘要翻译：本发明涉及寡核苷酸的化学合成以及可用于这种合成的化学实体。更具体地，本发明涉及寡核苷酸的核苷酸间键的硫化。本发明提供合成新的硫转移试剂的方法及其在硫化寡核苷酸中的用途。根据本发明的硫转移试剂制备成本低，储存稳定，溶解稳定，硫化效率高。

5. 发明授权

US06340749B1 Preparation of nucleoside phosphoramidites and oligonucleotide synthesis 失效
标题翻译：核苷亚磷酰胺的原位制备及寡核苷酸合成
公开(公告)号：US06340749B1
公开(公告)日：2002-01-22
申请号：US08647354
申请日：1996-05-09
申请人： Zhaoda Zhang , Jin-Yan Tang
发明人： Zhaoda Zhang , Jin-Yan Tang
IPC分类号： C07H2100
CPC分类号： C07H19/10 , C07F9/65038 , C07F9/6506 , C07F9/6518 , C07F9/65188 , C07F9/65583 , C07H19/20 , C07H21/00
摘要： The invention provides novel bifunctional phosphitylating reagents and their application in in situ preparation of 5′-protected nucleoside phosphoramidites and synthesis of oligonucleotides. Bifunctional phosphitylating reagents according to the invention react quickly with nucleosides under neutral or weakly basic conditions, without an additional activation step. In addition, the bifunctional phosphitylating reagents according to the invention generate chemoselectively the corresponding nucleoside phosphoramidites in situ, without need to purify the nucleoside phosphoramidites before using them in oligonucleotide synthesis. Finally, the bifunctional phosphitylating reagents according to the invention are relatively stable and easy to handle.
摘要翻译：本发明提供新型双功能磷酸化试剂及其在5'-保护的核苷亚磷酰胺的原位制备中的应用和寡核苷酸的合成。根据本发明的双功能磷酸化试剂在中性或弱碱性条件下与核苷快速反应，而没有额外的活化步骤。此外，根据本发明的双功能磷酸化试剂在原位生成相应的核苷亚磷酰胺，而不需要在寡核苷酸合成中使用之前纯化核苷亚磷酰胺。最后，本发明的双功能磷酸化试剂相对稳定且易于处理。

6. 发明授权

US5563253A Linear aminoalkylphosphoramidate oligonucleotide derivatives 失效
标题翻译：线性氨基烷基磷酰胺酸寡核苷酸衍生物
公开(公告)号：US5563253A
公开(公告)日：1996-10-08
申请号：US206175
申请日：1994-03-03
申请人： Sudhir Agrawal , Jin-Yan Tang
发明人： Sudhir Agrawal , Jin-Yan Tang
IPC分类号： C07H21/00 , C07H21/02 , C07H21/04 , C12Q1/68
CPC分类号： C07H21/00
摘要： Disclosed are methods of producing a synthetic oligonucleotide of selected nucleotide sequence which is internally functionalized at at least one selected location with an aminoalkyl-phosphoramidate and labelled with a nonradioactive material. Also disclosed are oligonucleotides produced by this method.
摘要翻译：公开了生产选择的核苷酸序列的合成寡核苷酸的方法，其在至少一个选择的位置用氨基烷基 - 氨基磷酸酯内部官能化并用非放射性物质标记。还公开了通过该方法制备的寡核苷酸。

7. 发明授权

US5541306A Aminoalkylphosphotriester oligonucleotide derivatives 失效
标题翻译：氨基烷基磷酸二酯寡核苷酸衍生物
公开(公告)号：US5541306A
公开(公告)日：1996-07-30
申请号：US357666
申请日：1994-12-16
申请人： Sudhir Agrawal , Jin-Yan Tang
发明人： Sudhir Agrawal , Jin-Yan Tang
IPC分类号： C07H21/00 , C07H21/02 , C07H21/04 , C12Q1/68
CPC分类号： C07H21/00
摘要： Disclosed are methods of producing a synthetic oligonucleotide of selected nucleotide sequence which is internally functionalized at least one selected location with an aminoalkylphosphotriester, and labelled with a nonradioactive material. Also disclosed are oligonucleotides produced by this method.
摘要翻译：公开了生产选择的核苷酸序列的合成寡核苷酸的方法，其在内部官能化至少一个选择的位置与氨基烷基磷酸三酯，并用非放射性物质标记。还公开了通过该方法生产的寡核苷酸。

8. 发明授权

US5536821A Aminoalkylphosphorothioamidate oligonucleotide deratives 失效
标题翻译：氨基烷基硫代氨基甲酸酯寡核苷酸衍生物
公开(公告)号：US5536821A
公开(公告)日：1996-07-16
申请号：US357399
申请日：1994-12-16
申请人： Sudhir Agrawal , Jin-Yan Tang
发明人： Sudhir Agrawal , Jin-Yan Tang
IPC分类号： C07H21/00 , C07H21/02 , C07H21/04 , C12Q1/68
CPC分类号： C07H21/00
摘要： Disclosed are methods of producing a synthetic oligonucleotide of selected nucleotide sequence which is internally functionalized at at least one selected location with an aminoalkylphosphorothioamidate and labelled with a nonradioactive material. Also disclosed are oligonucleotides produced by this method.
摘要翻译：公开了生产选定核苷酸序列的合成寡核苷酸的方法，其在至少一个选定位置用氨基烷基硫代氨基甲酸酯内部官能化并用非放射性物质标记。还公开了通过该方法制备的寡核苷酸。

9. 发明授权

US6096881A Sulfur transfer reagents for oligonucleotide synthesis 失效
标题翻译：用于寡核苷酸合成的硫转移试剂
公开(公告)号：US6096881A
公开(公告)日：2000-08-01
申请号：US865666
申请日：1997-05-30
申请人： Yongxin Han , Jimmy Tang , Zhoada Zhang , Jin-Yan Tang
发明人： Yongxin Han , Jimmy Tang , Zhoada Zhang , Jin-Yan Tang
IPC分类号： C07D285/12 , C07D285/125 , C07D285/135 , C07D285/16 , C07H21/00 , C07D285/01 , C07H21/02
CPC分类号： C07D285/16 , C07H21/00
摘要： In our research, two commercially available compounds, 3-amino-1,2,4-dithiazole-5-thione (1) and xanthane hydride (2), and their derivatives 3-6 are found to be potential sulfur-transfer reagents. The efficiency and optimization of these new sulfur-transfer reagents were investigated by solid-phase syntheses of dinudeotide and oligonucleotide phosphorothioates. The results show that both compounds 1 and 2 are highly efficient sulfurizing reagents, and better than 99% sulfur transfer efficiency can be achieved at each step. In contrast to Beaucage reagent, these novel sulfur-transfer reagents are very stable in various solvents, and are available in bulk quantities at low cost. Due to these advantages, compounds 1 and 2 can be considered alternatives to Beaucage reagent, especially in large-scale preparation of oligonucleotide phosphorothioates. Furthermore, compounds 1 and 2 were modified to enhance their solubility in acetonitrile. Three types of structure, as described as Formulae I, II, and III, are considered as potential efficient sulfur-transfer reagents based on our results.
摘要翻译：在我们的研究中，发现两种市售化合物，3-氨基-1,2,4-二噻唑-5-硫酮（1）和氢化蒽（2）及其衍生物3-6是潜在的硫转移试剂。通过二肽和寡核苷酸硫代磷酸酯的固相合成研究了这些新型硫转移试剂的效率和优化。结果表明，化合物1和化合物2均为高效硫化试剂，每步可达99％以上的硫转移效率。与Beaucage试剂相反，这些新型硫转移试剂在各种溶剂中非常稳定，并且可以以低成本批量获得。由于这些优点，化合物1和2可以被认为是拜耳试剂的替代物，特别是在大规模制备寡核苷酸硫代磷酸酯时。此外，化合物1和2被修饰以增强其在乙腈中的溶解度。根据我们的结果，三种类型的结构，如式I，II和III所述被认为是潜在的有效的硫转移试剂。

10. 发明授权

US5652103A Method for sequencing synthetic oligonucleotides containing non-phosphodiester internucleotide linkages 失效
标题翻译：用于测序含有非磷酸二酯核苷酸间键的合成寡核苷酸的方法
公开(公告)号：US5652103A
公开(公告)日：1997-07-29
申请号：US412913
申请日：1995-03-29
申请人： Sudhir Agrawal , Jin-Yan Tang
发明人： Sudhir Agrawal , Jin-Yan Tang
IPC分类号： C12N15/09 , C12Q1/68 , C12P19/34
CPC分类号： C12Q1/6855 , C12Q1/6869 , Y10T436/143333
摘要： The invention relates to synthetic oligonucleotides and more particularly to the determination of nucleotide sequences of synthetic oligonucleotides having non-phosphodiester internucleotide linkages. The invention provides a method for sequencing such modified synthetic oligonucleotides.
摘要翻译：本发明涉及合成的寡核苷酸，更具体地涉及确定具有非磷酸二酯核苷酸间键的合成寡核苷酸的核苷酸序列。本发明提供了对这种修饰的合成寡核苷酸进行测序的方法。

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