Liquid-phase process for preparing oligonucleotides
OwnerAndrew Livingston, Piers Robert James Gaffney +1inventors
InventorsAndrew Livingston, Piers Robert James Gaffney, Anna Livolsi
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Abstract
A membrane filtration-assisted, liquid-phase process for preparing oligonucleotides is described. The process addresses the disadvantages associated with the preparation, purification and storage of nucleoside phosphoramidites. The process of the invention allows for supported oligonucleotides of high purity to be grown from their constituent nucleosides in a stepwise manner, using simple nucleosides or short-chain oligonucleotides as the monomeric building blocks that are sequentially coupled to the supported growing oligonucleotide.
Claims25
A liquid-phase process for forming an oligonucleotide, the process comprising the steps of:
- a) providing a compound of formula I:
- wherein A is a nucleoside or an oligonucleotide, TA is a reactive terminal of the nucleoside or oligonucleotide, and Z is a soluble synthesis support to which the nucleoside or oligonucleotide is attached;
- b) modifying the compound of formula I to form a compound of formula II:
- in which A and Z are as defined in respect of formula I, X is a tertiary amino group and PG is a protecting group;
- c) isolating the compound of formula II by membrane filtration;
- d) providing a compound of formula III:
- wherein B is a nucleoside or an oligonucleotide, TB1 is a reactive terminal of the nucleoside or oligonucleotide, and TPG is a protected terminal of the nucleoside or oligonucleotide;
- e) reacting the compound of formula II with the compound of formula III to form a compound of formula IV:
- in which A and Z are as defined in respect of formula I, PG is as defined in respect of formula II, and B and TPG are as defined in respect of formula III.
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Dependencies are inferred from the claim text.