Purification of oligonucleotides
OwnerAchim H. Krotz, Vasulinga T. Ravikumarinventors
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Abstract
Methods and compounds useful for the purification of oligonucleotides and their analogs are provided wherein the oligonucleotides are contaminated with at least one oligonucleotide having at least one abasic site by the formation of imines at the aldehyde moiety of the abasic site and subsequent separation based on extractions, precipitations or chromatography.
Claims62
A method of purifying an oligonucleotide from a mixture, said mixture including said oligonucleotide and at least one contaminant comprising:
- treating said mixture with an amino reagent reactive with said contaminant for a time and under conditions effective to form an imine linkage with each said contaminant;
- and
- separating said oligonucleotide from said imine linked contaminants.
A method of purifying an oligonucleotide from a mixture, said mixture including said oligonucleotide and at least one contaminant, comprising:
- treating said mixture with a compound of formula I:
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- I
- wherein:
- x is from 0 to about 20,
- y is from 0 to about 5,
- n is from 0 to about 150,
- Z is a reactive nitrogenous moiety capable of reacting with an aldehyde to form an imine;
- for a time and under conditions effective to form an imine linkage with each contaminant;
- and
- separating said oligonucleotide from said imine linked contaminants.
A method of modifying the solubility of an oligonucleotide comprising:
- selecting an oligonucleotide having at least one abasic site;
- treating said oligonucleotide with an amino reagent reactive with said oligonucleotide for a time and under conditions effective to form an imine linkage between said oligonucleotide and said amino reagent at said abasic site.
A compound of Formula I,
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- x is from 0 to 20,
- y is from 0 to 5,
- n is from 0 to 150;
- and
- Z is —NH2, —NHNH2, —ONH2, —NHC(O)NHNH2 or —NHC(S)NHNH2.
Dependencies are inferred from the claim text.