专利号:US-9920084-B2 优先权日:2011-08-23 标题 :Ionic tags for synthesis of oligoribonucleotides 发明人:DAMHA MASAD J; HASSLER MATTHEW; CHAN TAK-HANG; NANDYALA MALLIKARJUNA REDDY; DONGA ROBERT ALEXANDER 权利人:DAMHA MASAD J; HASSLER MATTHEW; CHAN TAK HANG; NANDYALA MALLIKARJUNA REDDY; DONGA ROBERT ALEXANDER; THE ROYAL INSTITUTION FOR THE ADVANCEMENT OF LEARNING/MCGILL UNIV; HONG KONG POLYTECHNIC UNIV 摘要:The invention relates to the chemical synthesis of oligonucleotides, e.g., oligoribonucleotides. In another aspect, the invention relates to compounds of formula (II) processes for making these compounds, and the use thereof in the chemical synthesis of oligonucleotides, e.g., oligoribonucleotides. The invention also relates to methods of synthesis of oligomers, including but not limited to oligopeptides, oligosaccharides and oligonucleotides, particularly oligoribonucleotides and also oligodeoxyribonucleotides, in solution systems, and ionic tag linkers for use in methods provided herein.
专利号:US-9884885-B2 优先权日:2009-05-18 标题:Synthesis of labile base protected-modified deoxy and modified ribo nucleosides, corresponding phosphoramidites and supports and their use in high purity oligonucleotide synthesis 发明人:SRIVASTAVA SURESH C; SRIVASTAVA NAVEEN P 权利人:SRIVASTAVA SURESH C; SRIVASTAVA NAVEEN P; CHEMGENES CORP 摘要:This invention relates to novel method of synthesis of RNA utilizing N-2-acetyl protected guanine as nucleoside base, nucleosides, succinates, phosphoramidites, corresponding solid supports that are suitable for oligo deoxy nucleosides and RNA oligonucleotide synthesis. Our discovery using N-acetyl protected guanine as nucleoside base protecting group, which is significantly faster base labile protecting group, yet significantly more stable than commonly utilized-2-isobutyryl guanosine is a novel approach to obtain highest purity oligonucleotides. This approach is designed to lead to very high purity and very clean oligonucleotide, after efficient removal of the protecting groups, including acetyl group from guanine and to produce high purity therapeutic grade DNA oligonucleotides, RNA oligonucleotides, diagnostic DNA, diagnostic RNA for microarray platform. The deprotection of acetyl protecting groups of the natural deoxy and ribonucleosides occurs under substantially reduced time in contact with mild deprotection conditions such as mild bases, secondary amines for removal of such groups under such conditions would allows synthesis of various DNA and RNA of highest purity for diagnostics and therapeutic application. This approach is designed to lead to high purity large scale therapeutic grade oligonucleotide chimeras which consist of fluoro sugar modification in conjunction with deoxy nucleosides, ribonucleosides, modified base and modified sugar nucleosides. This approach is further designed to use acetyl guanine protecting group when other bases are sensitive nucleoside, and for use in oligo peptide synthesis and for support bound oligo nucleotides.
专利号:US-5824472-A 优先权日:1986-03-24 标 题 :Process for the synthesis of sugar nucleotides using recombinant-DNA methods 发明人:BETLACH MICHAEL R; DOHERTY DANIEL H; VANDERSLICE REBECCA W 权利人:MONSANTO CO 摘要:A recombinant-DNA mediated method for the synthesis of sugar nucleotides is disclosed. This method utilizes portable DNA sequences capable of directing the microbial synthesis of various enzymes that catalyze the synthesis of sugar nucleotides, including UDP-glucose, UDP-glucuronic acid and GDP-mannose. The sugar moieties of these sugar nucleotides may subsequently be incorporated into industrially-useful polysaccharides such as xanthan gum. It has been found that vectors containing the portable DNA sequences described herein are capable both of causing sugar nucleotide production in microorganisms previously incapable of such synthesis and of causing increased sugar nucleotide production in organisms capable of synthesizing small quantities of these compounds. In particular, plasmids pAS7, pAS9 and pTS13 are disclosed. These plasmids are capable of directing sugar nucleotide synthesis in various hosts, including Xanthomonas sp. such as X. campestris and other organisms such as E. coli and various Pseudomonas sp.
专利号:US-5714587-A 优先权日:1993-03-31 标 题 :Synthesis of anti-inflammatory compounds, and novel trisaccharides useful in the synthesis of anti-inflammatory compounds 发明人:LAINE ROGER A 权利人:UNIV LOUISIANA STATE; AGRICULTURAL AND MECHANICAL CO 摘要:Anti-inflammatory compounds are useful, for example, in treating arthritis and heart attack patients. Novel oligosaccharides useful in the rapid synthesis of certain anti-inflammatory compounds are disclosed, as is a rapid method of synthesizing the oligosaccharides. Low pH can loosen the acceptor specificity of galactosyltransferase (lactose synthase: EC 2.4.1.22), allowing the rapid synthesis of novel oligosaccharides. The disaccharides cellobiose (β1→4), laminaribiose (β1→3), gentiobiose (β1→6) and maltose (α1→4) acted as acceptors for lactose synthase under low pH conditions. From these four acceptors, the following four novel trisaccharides were synthesized: Gal p (β1→4)Glc p (β1→3) -Glc, Gal p (β1→4)Glc p (β1→4)-Glc, Gal p (β1→4)Glc p (β1→6)-Glc and Gal p (β1→4)Glc p (α1→4)Glc. These trisaccharides, and other oligosaccharides, may be synthesized in a few days with the disclosed technique, as opposed to the several months which would likely have been required with more traditional organic synthetic methods. These trisaccharides may be used as intermediates in the rapid synthesis of anti-inflammatory compounds.
专利号:US-2023235372-A1 优先权日:2020-06-12 标题:Ab-initio, template-independent synthesis of nucleic acids using thermostable enzymes 发明人:RANDRIANJATOVO-GBALOU IRINA; SAID AHMED; RAHIER RENAUD 权利人:SYNHELIX 摘要:The invention relates to the field of nucleic acid synthesis or sequencing, more specifically to methods for ab-initio synthesis of nucleic acids, comprising contacting a nucleotide with a free 3′-hydroxyl group, with at least one nucleoside triphosphate, or a combination of nucleoside triphosphates, in the presence of an archaeal DNA primase or a functionally active fragment and/or variant thereof, thereby covalently binding said nucleoside triphosphate to the free 3′-hydroxyl group of the nucleotide. It also relates to isolated functionally active fragments of archaeal DNA primases which are capable of both ab-initio single-stranded nucleic acid synthesis activity and template-independent terminal nucleotidyl transferase activity.
专利号:US-8981076-B2 优先权日:2008-11-29 标 题 :Synthesis of N-FMOC protected deoxy nucleosides, ribo nucleosides, modified deoxy and ribo nucleosides, and phosphoramidites, and their use in oligonucleotide synthesis 发明人:SRIVASTAVA SURESH C; SRIVASTAVA NAVEEN P 权利人:SRIVASTAVA SURESH C; SRIVASTAVA NAVEEN P; CHEMGENES CORP 摘要:This invention relates to synthesis of novel -N-FMOC protected nucleosides, succinates, phosphoramidites, corresponding solid supports that are suitable for oligo deoxy nucleosides and RNA oligonucleotide synthesis. Our discovery using N-FMOC as nucleoside base protecting group, which is highly base labile protecting group is a novel approach to obtain highest purity oligonucleotides. This approach is designed to lead to very high purity and very clean oligonucleotide, after efficient removal of the protecting groups and to produce high purity therapeutic grade DNA oligonucleotides, RNA oligonucleotides, diagnostic DNA, diagnostic RNA for microarray platform. The deprotection of FMOC protecting groups of the natural deoxy and ribonucleosides occurs under very mild deprotection conditions such as mild bases, secondary and tertiary amines for removal of such groups under such conditions would allows synthesis of various DNA and RNA of highest purity for diagnostics and therapeutic application. This approach is further designed to use FMOC protecting group on various base sensitive nucleoside, and for use in oligo peptide synthesis and for support bound oligo nucleotides. DNA oligonucleotides containing 3′-end dA at the 3′-terminal will be produced using the FMOC-dA-supports would lead to much reduced M−1 deletion sequences, and thereby high purity.
[参考文献]: Eric A Lee, Et Al. Targeting Mitochondria With Avocatin B Induces Selective Leukemia Cell Death. Cancer Res. 2015 Jun 15;75(12):2478-88. [参考文献]: Imen Lassoued, Et Al. Characterization, Antioxidative And Ace Inhibitory Properties Of Hydrolysates Obtained From Thornback Ray (Raja Clavata) Muscle. J Proteomics. 2015 Oct 14:128:458-68. [参考文献]: M Polo, Et Al. Mitochondrial (Dys)Function - A Factor Underlying The Variability Of Efavirenz-Induced Hepatotoxicity. Br J Pharmacol. 2015 Apr;172(7):1713-27. [参考文献]: S D Mesquita, Et Al. Lipocalin 2 Modulates The Cellular Response To Amyloid Beta. Cell Death Differ. 2014 Oct;21(10):1588-99. [参考文献]: Sang-Yong Lee, Et Al. Polyoxometalates--Potent And Selective Ecto-Nucleotidase Inhibitors. Biochem Pharmacol. 2015 Jan 15;93(2):171-81.
合成参考文献
参考文献:10.1007/s00432-010-0812-0 摘要:Xu S, Yan P, Shao Z. Differential proteomic analysis of a highly metastatic variant of human breast cancer cells using two-dimensional differential gel electrophoresis. Journal of Cancer Research and Clinical Oncology. 2010 Feb 14;136(10):1545–56. doi: 10.1007/s00432-010-0812-0. 参考文献:10.1007/s00232-010-9229-6 摘要:Kwak Y, Högbom M, Colque-Navarro P, Möllby R, Vécsey-Semjén B. Biological Relevance of Natural α-Toxin Fragments from Staphylococcus aureus. The Journal of Membrane Biology. 2010 Feb 14;233(1-3):93–103. doi: 10.1007/s00232-010-9229-6. 参考文献:10.1007/s00018-011-0762-y 摘要:Bratkovič T, Rogelj B. Biology and applications of small nucleolar RNAs. Cellular and Molecular Life Sciences. 2011 Jul 12;68(23):3843–51. doi: 10.1007/s00018-011-0762-y. 参考文献:10.1007/978-1-61779-188-8_11 摘要:Li L, Liu Y. Diverse small non-coding RNAs in RNA interference pathways. Methods Mol Biol. 2011;764():169–82. doi: 10.1007/978-1-61779-188-8_11.