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US 5,770,713 AGranted
Phosphorothioate triester oligonucleotides and method of preparation
AssigneeCentre National De La Recherche Scientifique
InventorsJean-Louis Imbach, Bernard Rayner
Life of this patent
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Abstract
The trister phosphorothioate oligonucleotides disclosed comprise internucleotide concatenations having a P--S.sup.- bond protected by a bioreversible grouping (X) in intracellular media.
Claims35
An oligonucleotide comprising the general formula ##STR14## in which:
- Y is O or S;
- R.sub.1 and R.sub.2 are, respectively, a residue in the 3' -O and 5' -O positions of a nucleoside or of an oligonucleotide, the internucleotide linkage of which is natural or modified;
- X is --(CH.sub.2).sub.n --S--S--U, --(CH.sub.2).sub.n --O--C (.dbd.Y.sup.2)--Z or --(CH.sub.2).sub.n --S--C(.dbd.O) --Z;
- each n is independently an integer from 1 to 6;
- U is an optionally substituted alkyl, aryl or sugar residue;
- Y.sup.2 is O or S;
- and
- Z is optionally substituted alkyl or sugar residue.
5 more elements
An oligonucleotide comprising the general formula ##STR15## in which:
- Y is O or S;
- R.sub.1 and R.sub.2 are respectively a residue in the 3' -O and 5' -O positions of a nucleoside or of an oligonucleotide, the internucleotide linkage of which is natural or modified;
- X is a --(CH.sub.2).sub.n --Y.sup.1 --W radical, where
- y.sup.1 is S or O;
- each n is independently an integer from 1 to 6;
- and
- W is either SU or --C(Y.sup.2)--Z, where U and Z are a lower alkyl, optionally substituted by one or more groups selected from the group consisting of OH, SH and NH.sub.2, and where Y.sup.2 is O or S.
4 more elements
An oligonucleotide comprising the general formula ##STR19## in which:
- Y is O or S;
- R.sub.1 and R.sub.2 are respectively a residue in the 3' -O and 5' -O positions of a nucleoside or of an oligonucleotide, the internucleotide linkage of which is natural or modified;
- X is a --(CH.sub.2).sub.n --Y.sup.1 --W radical where
- Y.sup.1 is S or O;
- each n is independently an integer from 1 to 6;
- and
- W is either SU or --C(Y.sup.2)--Z, where
- U is an optionally substituted alkyl, aryl or sugar residue;
- Y.sup.2 O or S;
- and
- Z is an optionally substituted alkyl, aryl or sugar residue;
- wherein R.sub.1 and R.sub.2 have electrically neutral sequences at the 5' and 3' ends respectively, which are resistant to degradation by exonucleases;
- and
- wherein the internucleotide linkages at the 5' and 3' ends respectively of R.sub.1 and R.sub.2 are of the methylphosphonate type.
11 more elements
An oligonucleotide comprising the general formula ##STR20## in which:
- Y is O or S;
- R.sub.1 and R.sub.2 are respectively a residue in the 3' -O and 5' -O positions of a nucleoside or of an oligonucleotide, the internucleotide linkage of which is natural or modified;
- X is a --(CH.sub.2).sub.n --Y.sup.1 --W radical where
- Y.sup.1 is S or O;
- each n is independently an integer from 1 to 6;
- and
- W is either SU or --C(Y.sup.2)--Z, where
- U is an optionally substituted alkyl, aryl or sugar residue;
- Y.sup.2 is O or S;
- and
- Z is an optionally substituted alkyl, aryl or sugar residue;
- wherein said oligonucleotide is formed from a chimeric oligomer comprising a .beta.-anomeric central DNA or RNA sequence, the internucleotide linkages of which are of the ##STR21## type, this central sequence being flanked in the 5' and 3' positions by .alpha.-anomeric DNA or RNA.
9 more elements
An oligonucleotide comprising the general formula ##STR28## in which:
- Y is O or S;
- R.sub.1 and R.sub.2 are respectively a residue in the 3' -O and 5' -O positions of a nucleoside or of an oligonucleotide, the internucleotide linkage of which is natural or modified;
- X is a --(CH.sub.2).sub.n --Y.sup.1 --W radical where
- Y.sup.1 is S or O;
- each n is independently an integer from 1 to 6;
- and
- W is either SU or --C(Y.sup.2)--Z, where
- U is an optionally substituted alkyl, aryl or sugar residue;
- Y.sup.2 O or S;
- and
- Z is an optionally substituted alkyl, aryl or sugar residue;
- characterized in that said oligonucleotide is formed from a chimeric oligomer comprising a beta-anomeric central DNA or RNA sequence, the internucleotide linkages of which have the formula ##STR29## this central sequence being flanked in the 5' and 3' positions by alpha-anomeric DNA or RNA.
9 more elements
A phosphorothioate triester oligonucleotide comprising internucleotide linkages which have a P--S bond wherein the S moiety thereof is protected by a group comprising a carbonyl-containing moiety;
- and
- wherein said carbonyl-containing moiety is of the formula --(CH.sub.2).sub.n --Y.sup.1 --W wherein:
- Y.sup.1 is S or O;
- each n is independently an integer from 1 to 6;
- and
- W is -C(Y.sup.2)Z where Y.sup.2 is O or S;
- and
- Z is optionally substituted alkyl or a sugar residue.
5 more elements
An oligonucleotide comprising the general formula ##STR35## in which:
- Y is O;
- R.sub.1 and R.sub.2 are, respectively, a residue in the 3' -O and 5' -O positions of a nucleoside or of an oligonucleotide, the internucleotide linkage of which is natural or modified;
- X is --(CH.sub.2).sub.n --S--S--U, --(CH.sub.2).sub.n --O--C(.dbd.Y.sup.2)--Z or --(CH.sub.2).sub.n --S--C(.dbd.O)--Z;
- each n is independently an integer from 1 to 6;
- U is an optionally substituted alkyl, aryl or sugar residue;
- Y.sup.2 is O or S;
- and
- Z is optionally substituted alkyl, aryl or sugar residue.
5 more elements
An oligonucleotide comprising the general formula ##STR36## in which:
- Y is O or S;
- R.sub.1 and R.sub.2 are, respectively, a residue in the 3' -O and 5' -O positions of a nucleoside or of an oligonucleotide, the internucleotide linkage of which is natural or modified;
- X is --(CH.sub.2).sub.n --S--S--U or --(CH.sub.2).sub.n --O--C(.dbd.Y.sup.2)--Z;
- each n is independently an integer from 1 to 6;
- U is an optionally substituted alkyl, aryl or sugar residue;
- Y.sup.2 is O or S;
- and
- Z is optionally substituted alkyl, aryl or sugar residue.
5 more elements
Dependencies are inferred from the claim text.