Synthetic catalytic oligonucleotide structures

Claim 2

An oligonucleotide structure with a catalytically active center which has a hammerhead structure, having the general structural formula (II): ##STR9## wherein x and y can be the same or different and x≧1 and y≧2, N 5 and N 6 are in each case nucleotides which are complementary to one another and * represents a base pairing, N' and N" either represent two nucleotide sequences which contain nucleotides which are at least partially complementary to one another so as to enable a stable base pairing between the two nucleotide sequences or N' and N" together represent a single nucleotide sequence whereby at least part of the sequence can form a double-stranded stem at least part of the sequence can form a double-stranded stem by base pairing between complementary nucleotides, and in which, at least one additional nucleotide N can be inserted after N 7 or/and N 9 ; the residue R in formula (I) is different from hydrogen in at least one of the nucleotides N 2 , N 3 , N 5 , N 6 , N 7 , N 9 , N 10 , N 12 , N 13 and N 14 in formula (II), and N in each case represents a nucleotide according to the general structural formula (I) ##STR10## wherein B represents a nucleoside base which is selected from the group consisting of adenin-9-yl (A), cytosin-1-yl (C), guanin-9-yl (G), uracil-1-yl (U), uracil-5-yl (ψ), hypoxanthin-9-yl (I), thymin-1-yl (T) and 2-aminoadenin-9-yl, V in each nucleotide is independently an O or a CH 2 group, X and W can in each nucleotide be the same different and are independently O, S, NH 2 , alkyl or alkoxy groups with 1 to 10 carbon atoms, and R is hydrogen or a straight-chained or branched alkyl, alkenyl or alkinyl group with 1 to 10 carbon atoms which is unsubstituted or substituted with halogen, cyano, isocyano, nitro, amino, carboxyl, hydroxyl or/and mercapto groups.

Claim 3

Oligonucleotide structure as claimed in claim 1 wherein the residues R in formula (I) are hydrogen in the nucleotides N 1 , N 4 , N 8 and N 11 .

Claim 4

Oligonucleotide structure as claimed in claim 1, wherein the residues V, W and X in formula (I) and O groups.

Claim 5

Oligonucleotide structure as claimed in claim 1, wherein the residues R in formula (I) which are different from hydrogen contain 1 to 6 carbon atoms.

Claim 6

Oligonucleotide structure as claimed in claims 4, wherein the residues R in formula (I) which are different from hydrogen are selected from the group comprising methyl, ethyl, propyl, allyl, dimethylallyl, butyl or cyanomethyl residues.

Claim 7

Oligonucleotide structure as claimed in claim 1 having the general structural formula (III): ##STR11## in which N, x and y are as previously defined M represents a chemical bond or denotes a nucleotide sequence (N) a , whereby a ≧1, m and n are the same or different and, if desired, one or several additional nucleotides can be inserted after N 7 or/and N 9 .

Claim 8

Oligonucleotide structure as claimed in claim 6 wherein the residues R in formula (III) are hydrogen in the nucleotides N 1 , N 4 , N 8 , N 10 , N 11 and N 12 .

Claim 9

Oligonucleotide structure as claimed in claim 6, wherein the residues R in formula (III) are different from hydrogen in all nucleotides apart from N 1 , N 4 , N 8 , N 10 , N 11 and N 12 .

Claim 10

Oligonucleotide structure as claimed in claim 1, wherein the residues V, W and X in formula (I) are O groups and the residues B and R in formula (I) or (III) have the following meanings for the nucleotides N 1 to N 14 : N 1 : B=A and R=H, N 2 : B=A and R=allyl, N 3 : B=A and R=allyl, N 4 : B=G and R=H, N 5 : B=C and R=allyl, N 6 : B=G and R=allyl, N 7 : B=A and R=allyl, N 8 : B=G and R=H, N 9 : B=U and R=allyl, N 10 : B=A and R=H, N 11 : B=G and R=H, N 12 : B=U and R=H, N 13 : B=C and R=allyl, N 14 : B=U and R=allyl.

Claim 11

Oligonucleotide structure as claimed in claim 1, wherein the residues V, W and X in formula (I) are O groups with the exception that the linkage between N 11 and N 12 is a phosphorothioate group (X=O and W=S) and the residues B and R in formula (I) or (III) have the meaning according to claim 12 for the nucleotides N 1 to N 14 .

Claim 12

Oligonucleotide structure as claimed in claim 1, wherein the residues V, W and X in formula (I) are O groups and the residues B in formula (I) or (III) have the meaning according to claim 12 for the nucleotides N 1 to N 14 and R=H for N 1 , N 4 , N 8 , N 10 , N 11 and N 12 , R=3,3-dimethylallyl for N 9 and R=allyl for N 2 , N 3 , N 5 , N 6 , N 7 , N 13 and N 14 .

Claim 13

Oligonucleotide structure as claimed in claim 1, wherein the residues V, W and X in formula (I) are O groups and the residues B in formula (I) or (III) have the meaning according to claim 12 for the nucleotides N 1 to N 14 and R=H for N 1 , N 4 , N 8 , N 10 , N 11 and N 12 , R=3,3-dimethylallyl for N 3 and R=allyl for N 2 , N 5 , N 6 , N 7 , N 9 , N 13 and N 14 .

Claim 14

Oligonucleotide structure as claimed in claim 1, wherein the residues V, W and X in formula (I) are O groups and the residues B in formula (I) or (III) have the meaning according to claim 12 for the nucleotides N 1 to N 14 and R=H for N 1 , N 4 , N 8 , N 10 , N 11 and N 12 , R=cyanomethyl for N 2 , N 3 , N 7 , N 9 and N 13 and R=allyl for N 5 , N 6 and N 14 .

Claim 15

Oligonucleotide structure as claimed in claim 1, wherein the residues V, W and X in formula (I) are O groups and the residues B in formula (I) or (III) have the meaning according to claim 12 for the nucleotides N 1 to N 14 and R=H for N 1 , N 4 , N 8 , N 10 , N 11 and N 12 , R=butyl for N 5 and N 6 and R=allyl for N 2 , N 3 , N 7 , N 9 , N 13 and N 14 whereby, if desired, R=butyl in one or several of the residues N that are present in a base-paired form in formula (III).

Claim 16

Oligonucleotide structure as claimed in claim 1, wherein it is linked to a prosthetic group selected from polyamino acids, lipids, hormones or peptides in order to improve the uptake into the cell or/and the specific cellular localization of the oligonucleotide structure.

Claim 17

Diagnostic reagent, wherein it contains an oligonucleotide structure as claimed in claim 1 as a constituent.

Claim 18

An oligonucleotide structure with a catalytically active center which has a hammerhead structure, having the general structural formula (II): ##STR12## wherein x and y can be the same or different and x≧1 and y≧2, N 5 and N 6 are in each case nucleotides which are complementary to one another and * represents a base pairing, N' and N" either represent two nucleotide sequences which contain nucleotides which are at least partially complementary to one another so as to enable a stable base pairing between the two nucleotide sequences or N' and N" together represent a single nucleotide sequence whereby at least part of the sequence can form a double-stranded stem by base pairing between complementary nucleotides, wherein, at least one additional nucleotide N can be inserted after N 7 or/and N 9 ; and N in each case represents a nucleotide according to the general structural formula (I) ##STR13## in which B represents a nucleoside base which is in particular selected from the group consisting of adenin-9-yl (A), cytosin-1-yl (C), guanin-9-yl (G), uracil-1-yl (U), uracil-5-yl (ψ), hypoxanthin-9-yl (I), thymin-1-yl (T) and 2-aminoadenin-9-yl, N 1 : B=A or an A-analogue N 2 : B=A or an A-analogue N 3 : B=A or an A-analogue N 4 : B=G or an G-analogue N 7 : B=A or an A-analogue N 8 : B=G or an G-analogue N 9 : B=U N 10 : B=A or an A-analogue N 11 : B=G or an G-analogue N 12 : B=U N 13 : B=C N 14 : B=U V in each nucleotide is independently an O or a CH 2 group, X and W can in each nucleotide be the same or different and are independently O, S, NH 2 , alkyl or alkoxy groups with 1 to 10 carbon atoms, and R is hydrogen or a straight-chained or branched alkyl, alkenyl or alkinyl group with 1 to 10 carbon atoms which is unsubstituted or substituted with halogen, cyano, isocyano, nitro, amino, carboxyl, hydroxyl or/and mercapto groups, wherein in at least one of the nucleotides the residue R in formula (I) is different from hydrogen.

Claim 19

An oligonucleotide structure with a catalytically active center which has a hammerhead structure, having the general structural formula (II): ##STR12## wherein x and y can be the same or different and x≧1 and y≧2, N 5 and N 6 are in each case nucleotides which are complementary to one another and * represents a base pairing, N' and N" either represent two nucleotide sequences which contain nucleotides which are at least partially complementary to one another so as to enable a stable base pairing between the two nucleotide sequences or N' and N" together represent a single nucleotide sequence whereby at least part of the sequence can form a double-stranded stem by base pairing between complementary nucleotides, wherein, at least one additional nucleotide N can be inserted after N 7 or/and N 9 ; and N in each case represents a nucleotide according to the general structural formula (I) ##STR13## in which B represents a nucleoside base which is in particular selected from the group consisting of adenin-9-yl (A), cytosin-1-yl (C), guanin-9-yl (G), uracil-1-yl (U), uracil-5-yl (ψ), hypoxanthin-9-yl (I), thymin-1-yl (T) and 2-aminoadenin-9-yl, N 1 : B=A or an A-analogue N 2 : B=A or an A-analogue N 3 : B=A or an A-analogue N 4 : B=G or an G-analogue N 7 : B=A or an A-analogue N 8 : B=G or an G-analogue N 9 : B=U N 10 : B=A or an A-analogue N 11 : B=G or an G-analogue N 12 : B=U N 13 : B=C N 14 : B=U V in each nucleotide is independently an O or a CH 2 group, X and W can in each nucleotide be the same or different and are independently O, S, NH 2 , alkyl or alkoxy groups with 1 to 10 carbon atoms, and R is hydrogen or a straight-chained or branched alkyl, alkenyl or alkinyl group with 1 to 10 carbon atoms which is unsubstituted or substituted with halogen, cyano, isocyano, nitro, amino, carboxyl, hydroxyl or/and mercapto groups, wherein in at least one of the nucleotides the residue R in formula (I) is different from hydrogen.

Claim 20

An oligonucleotide structure according to claim 1 wherein B in nucleotide N 1 is selected from the group consisting of adenin-9-yl (A) and 2-aminoadenin-9-yl and B in nucleotides N 4 , N 8 , and N 11 is guanin-9-yl (G).

Claim 21

An oligonucleotide structure according to claim 1, wherein 3'deoxyribonucleotides and/or 3'-O-alkylribonucleotides are present at a free 3' end of the oligonucleotide structure.

Claim 22

A pharmaceutical agent comprising the oligonucleotide according to claim 1 in combination with a pharmaceutically acceptable carrier.

Claim 23

An oligonucleotide structure according to claim 1, wherein X and W can in each nucleotide be the same or different and are independently O, S, NH 2 , alkyl or alkoxy groups with 1 to 4 carbon atoms.