发明名称 |
Processes and reagents for oligonucleotide synthesis and purification |
摘要 |
The present invention relates to processes and reagents for oligonucleotide synthesis and purification. One aspect of the present invention relates to compounds useful for activating 5 phosphoramidites in oligonucleotide synthesis. Another aspect of the present invention relates to a method of preparing oligonucleotides via the phosphoramidite method using an activator of the invention. Another aspect of the present invention relates to sulfur-transfer agents. In a preferred embodiment, the sulfur-transfer agent is a 3-amino 1,2,4-dithiazolidine-5-one. Another aspect of the present invention relates to a 10 method of preparing a phosphorothioate by treating a phosphite with a sulfur-transfer reagent of the invention. In a preferred embodiment, the sulfur-transfer agent is a 3-amino-1,2,4dithiazolidine-5-one. Another aspect of the present invention relates to compounds that scavenge acrylonitrile produced during the deprotection of phosphate groups bearing ethylnitrile protecting groups. In a preferred embodiment, the acrylonitrile 15 scavenger is a polymer-bound thiol. Another aspect of the present invention relates to agents used to oxidize a phosphite to a phosphate. In a preferred embodiment, the oxidizing agent is sodium chlorite, chloroamine, or pyridine-N-oxide. Another aspect of the present invention relates to methods of purifying an oligonucleotide by annealing a first single-stranded oligonucleotide and seond single-stranded oligonucleotide to form a 20 double-stranded oligonucleotide; and subjecting the double-strandged oligonucleotide to chromatographic purification. In a preferred embodiment, the chromatographic purification is highperformance liquid chromatography. 2715856.i (GHMatters) P62274.AU.1 |
申请公布号 |
AU2011203074(A1) |
申请公布日期 |
2011.07.14 |
申请号 |
AU20110203074 |
申请日期 |
2011.06.23 |
申请人 |
ALNYLAM PHARMACEUTICALS, INC. |
发明人 |
MANOHARAN, MUTHIAH;JUNG, MICHAEL E.;RAJEEV, KALLANTHOTTATHIL G.;PANDEY, RAJENDRA K.;WANG, GANG |
分类号 |
C07C321/20;C07D249/04;C07D249/08;C07D249/10;C07D249/18;C07D257/04;C07D285/00;C07D285/01;C07F9/09;C07F9/141;C07F9/165;C07H21/00 |
主分类号 |
C07C321/20 |
代理机构 |
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代理人 |
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主权项 |
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地址 |
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