Method of preventing modification of synthetic oligonucleotides
OwnerNanda Sinhainventor
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Abstract
The present invention relates to a method of preventing modification of a synthetic oligonucleotide or oligonucleotide analog during removal of at least one cyanoethyl protecting group from the oligonucleotide or oligonucleotide analog. The method involves contacting the oligonucleotide or oligonucleotide analog with a basic solution having at least one acrylonitrile scavenger, such as t-butylamine, at a sufficient temperature and for a sufficient period of time to remove at least one β-cyanoethyl protecting group. The present invention also relates to a method of producing a synthetic oligonucleotide or oligonucleotide analog.
Claims20
A method of substantially preventing modification of a synthetic oligonucleotide or an oligonucleotide analog during cleavage of at least one β-cyanoethyl protecting group from the oligonucleotide or oligonucleotide analog, comprising the step of contacting a β-cyanoethyl protected oligonucleotide or oligonucleotide analog with an organic solution comprising a nitrile solvent and at least one acrylonitrile scavenger under conditions sufficient to remove at least one β-cyanoethyl protecting group, provided that when the acrylonitrile scavenger comprises a primary aliphatic amine or a primary aliphatic thiol, the primary aliphatic amine or the primary aliphatic thiol is sterically hindered.
A method of producing an oligonucleotide or oligonucleotide analog, wherein modification of the oligonucleotide or oligonucleotide analog during removal of the β-cyanoethyl protecting group is substantially prevented, comprising the steps of:
- a) synthesizing an oligonucleotide or oligonucleotide analog having at least one β-cyanoethyl protecting group;
- and
- b) contacting the β-cyanoethyl protected oligonucleotide or oligonucleotide analog with an organic solution comprising a nitrile solvent and at least one acrylonitrile scavenger under conditions sufficient to remove at least one β-cyanoethyl protecting group, provided that when the acrylonitrile scavenger comprises a primary aliphatic amine or a primary aliphatic thiol, the primary aliphatic amine or the primary aliphatic thiol is sterically hindered.
A method of producing an oligonucleotide or oligonucleotide analog comprising the steps of:
- a) synthesizing an oligonucleotide or oligonucleotide analog having at least one β-cyanoethyl protecting group;
- and
- b) contacting the β-cyanoethyl protected oligonucleotide or oligonucleotide analog with a solution comprising acetonitrile and t-butylamine under conditions sufficient to remove at least one β-cyanoethyl protecting group.
Dependencies are inferred from the claim text.