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http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C12N15-113
filingDate 2019-12-23-04:00^^<http://www.w3.org/2001/XMLSchema#date>
grantDate 2020-12-29-04:00^^<http://www.w3.org/2001/XMLSchema#date>
inventor http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_eea02c6a68201edbb9faebfd1654be58
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publicationDate 2020-12-29-04:00^^<http://www.w3.org/2001/XMLSchema#date>
publicationNumber RU-2738093-C9
titleOfInvention Synthesis method of 2'-o-(2-methoxyethyl) thiophosphate oligonucleotide
abstract FIELD: biotechnology.SUBSTANCE: invention relates to biotechnology, particularly to a novel method of producing antisense compounds which can be used as pharmaceutical substances for ameliorating the symptoms of spinal muscular atrophy. Disclosed method of producing modified thiophosphate oligonucleotide containing 2'-O-(2-methoxyethyl) ribonucleotides of structure UCACUUUCAUAAUGCUGG, where each nucleoside contains 2 ' -O- (2-methoxyethyl) modified sugar residue provides for synthesis of oligonucleotide on a solid-phase support using an amidophosphite method. To obtain thiophosphate groups, 3-[(dimethylaminomethylene)amino]-3H-1,2,4-dithiazol-5-thione (DDTT) is used in 30 % solution of pyridine in acetonitrile, release is performed by adding a saturated ammonia solution in the presence of disodium salt of ethylenediaminetetraacetic acid for 3 days at room temperature. Method then includes successively purifying oligonucleotides by ion exchange chromatography on Tosoh Super-Q 5PW column using Tris-HCl buffer, pH 7.0, with addition of 10 % acetonitrile in water, and then Tris-HCl buffer, pH 7.0, with addition of sodium perchlorate and 10 % acetonitrile in water, by reversed-phase chromatography on Waters xBridge WEN C18 column using a buffer, which is a solution of triethylammonium acetate in water, pH 7.0, and then a buffer which is a solution of triethylammonium acetate in 80 % aqueous solution of acetonitrile, pH 7.0, and gel filtration followed by extraction of the end product with drying by lyophilisation.EFFECT: invention enables to obtain a product with higher degree of purification.1 cl, 8 dwg, 4 tbl, 2 ex
priorityDate 2019-12-23-04:00^^<http://www.w3.org/2001/XMLSchema#date>
type http://data.epo.org/linked-data/def/patent/Publication

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