Improved methods for oligonucleotide synthesis

专利名称：Improved methods for oligonucleotide

synthesis

发明人：DOUGLAS ALAN LIVINGSTON申请号：AU5752496申请日：19960516公开号：AU694359B2公开日：19980716

摘要：Improved methods for solution-phase synthesis of purified short-chain

oligonucleotide coupling units, such as dimers, trimers, and tetramers, suitable for use insolution-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 firstsegments comprising one, two, three, four, six or eight nucleosides, and each of said firstsegments 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 firstsegments comprising one, two, three, four, six or eight nucleosides, each of said secondsegments having two non-identical reactive functional groups, b and c, which are asecondary alcohol group and a primary alcohol group, respectively; and (c) reacting saidfirst and second segments in solution to produce a first linkage isomer, YZ-b, whichretains 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 saidYZ 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 linkageisomer is selectively capped.

申请人：LA JOLLA PHARMACEUTICAL COMPANY

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