专利号:US-8138330-B2 优先权日:2006-09-11 标 题 :Process for the synthesis of oligonucleotides 发明人:LEUCK MICHAEL; WOLTER ANDREAS; STUMPE ALFRED 权利人:LEUCK MICHAEL; WOLTER ANDREAS; STUMPE ALFRED; SIGMA ALDRICH CO LLC 摘要:The present invention discloses novel methods for the synthesis of oligonucleotides with nucleoside phosphoramidites on solid supports. The methods comprise the stepwise chain assembly of oligonucleotides on supports with 5′-acyl phosphoramidites. The synthesis cycles consist of a front end deprotection step which is conducted with a solution of a primary amine or a phenolate, a phosphoramidite coupling step with a 5′-acyl nucleoside phosphoramidite in the presence of an activator, a phosphite oxidation step and an optional capping step. The novel methods improve the quality of synthetic oligonucleotides due to the irreversibility of the front end deprotection step, which prevents the formation of deletion sequences, and due to the avoidance of acidic reagents in the synthesis cycles, which prevent the formation of depurination side products. The invention further discloses novel nucleoside phosphoramidite compositions wherein the phosphoramidites carry acyl front end protective groups which are cleavable with primary amines or phenolates. The invention is applicable to the synthesis of oligodeoxyribonucleotides, oligoribonucleotides and oligonucleotides with modifications in their sugar or phosphate groups.
专利号:WO-2025044766-A1 优先权日:2023-08-31 标题:Use of silicon dioxide microspheres in synthesis of ultra-long oligonucleotide and method for synthesizing ultra-long oligonucleotide 发明人:SHI YONGYONG; ZHANG MANCANG; WANG LIBING; GAO PANPAN; FANG JUN 权利人:UNIV SHANGHAI JIAOTONG; SHANGHAI DYNEGENE TECH CO LTD 摘要:The present invention relates to the technical field of oligonucleotide synthesis. Disclosed are the use of silicon dioxide microspheres in the synthesis of an ultra-long oligonucleotide and a method for synthesizing an ultra-long oligonucleotide, wherein the silicon dioxide microspheres have a specific surface area of less than 1 m2/g, and preferably, the silicon dioxide microspheres have modification groups on the surface. The method for synthesizing an ultra-long oligonucleotide comprises: performing a coupling reaction on a nucleoside phosphoramidite synthesis unit using the silicon dioxide microspheres having modification groups on the surface as carriers under coupling reaction conditions. The prepared carriers can be used to prepare an ultra-long oligonucleotide.
专利号:US-10167308-B2 优先权日:2013-09-14 标题:Highly efficient synthesis of long RNA using reverse direction approach 发明人:SRIVASTAVA SURESH C; SRIVASTAVA NAVEEN P 权利人:CHEMGENES CORP 摘要:The present invention relates to novel process of reverse 5′→3′ directed synthesis of RNA oligomers in the range of about 100-mer to about 200-mer has been developed and disclosed. Using that method demonstrated high quality RNA synthesis with coupling efficiency approaching 99%.
专利号:US-6262251-B1 优先权日:1995-10-19 标题 :Method for solution phase synthesis of oligonucleotides 发明人:PIEKEN WOLFGANG; MCGEE DANNY; SETTLE ALECIA; ZHAI YANSHENG; HUANG JIANPING 权利人:PROLIGO LLC 摘要:This invention discloses an improved method for the sequential solution phase synthesis of oligonucleotides. The method lends itself to automation and is ideally suited for large scale manufacture of oligonucleotides with high efficiency.
专利号:WO-9847910-A1 优先权日:1997-04-21 标题:Method for solution phase synthesis of oligonucleotides 发明人:PIEKEN WOLFGANG; MCGEE DANNY; SETTLE ALECIA; ZHAI YANSHENG; HUANG JIANPING; HILL KEN; SMITH RANDALL S 权利人:NEXSTAR PHARMACEUTICALS INC; PIEKEN WOLFGANG; MCGEE DANNY; SETTLE ALECIA; ZHAI YANSHENG; HUANG JIANPING; HILL KEN; SMITH RANDALL S 摘要:This invention discloses an improved method for the sequential solution phase synthesis of oligonucleotides. The method lends itself to automation and is ideally suited for large scale manufacture oligonucleotides with high efficiency.
专利号:US-5874532-A 优先权日:1997-01-08 标 题 :Method for solution phase synthesis of oligonucleotides and peptides 发明人:PIEKEN WOLFGANG; GOLD LARRY 权利人:NEXSTAR PHARMACEUTICALS INC 摘要:This invention discloses an improved method for the sequential solution phase synthesis of oligonucleotides and peptides. The method lends itself to automation and is ideally suited for large scale manufacture oligonucleotides with high efficiency.