Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives
Patent
1998-12-16
2000-12-26
Wilson, James O.
Organic compounds -- part of the class 532-570 series
Organic compounds
Carbohydrates or derivatives
536 243, 536 2432, 536 2531, 536 2532, 536 2533, 536 2534, 536 254, 536 2541, 536 256, C07H 2104
Patent
active
061661988
ABSTRACT:
Improved methods for solution-phase synthesis of purified short-chain oligonucleotide coupling units, such as dimers, trimers, and tetramers, suitable for use in solution-phase or solid-phase oligonucleotide synthesis are provided. In one embodiment, there is provided methods of preparing a coupled oligonucleotide, YZ, comprising: (a) providing first nucleotidic segments, Y, in solution, each of the first segments comprising one, two, three, four, six or eight nucleosides, and each of said first segments having a reactive functional group, a, which is a phosphoramidite group; (b) providing a plurality of second nucleotidic segments, Z, in solution, each of said first segments comprising one, two, three, four, six or eight nucleosides, each of said second segments having two non-identical reactive functional groups, b and c, which are a secondary alcohol group and a primary alcohol group, respectively; and (c) reacting said first and second segments in solution to produce a first linkage isomer, YZ-b, which retains a residual secondary alcohol group, b, and a non-identical second linkage isomer, YZ-c, which retains a residual primary alcohol group, c; and (d) reacting a mixture of said YZ linkage isomers, or derivatives thereof, with a selective capping reagent, in solution, whereby said residual secondary alcohol group, b, of said YZ-b linkage isomer remains selectively unchanged, and the residual primary alcohol group, c, of said YZ-c linkage isomer is selectively capped.
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La Jolla Pharmaceutical Company
Wilson James O.
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