RU2001128167A

RU2001128167A - XILO-ZNK ANALOGUES

Info

Publication number: RU2001128167A
Application number: RU2001128167/04A
Authority: RU
Inventors: Еспер ВЕНГЕЛЬ
Original assignee: Эксикон А/С
Priority date: 1999-03-18
Filing date: 2000-03-17
Publication date: 2003-07-20

Claims

1. An oligomer comprising at least one nucleoside analog in the xyl configuration of general formula I

where X is selected from —O—, —S—, —N (R ^{N *} ) -, —C (R ⁶ R ^{6 *} ) -;

B is selected from hydrogen, hydroxy, optionally substituted C _1-4 alkoxy, optionally substituted C _1-4 alkyl, optionally substituted C _1-4 acyloxy, nucleotide bases, DNA intercalators, photochemically active groups, thermochemically active groups, chelating groups reporter groups and ligands;

P denotes the position of the radical in the intranucleoside ligament relative to the preceding monomer or 5'-terminal group, such an intranucleoside ligament or 5'-terminal group optionally includes a substituent R ⁵ or an equally acceptable substituent R ^{5 *} ;

P ^* denotes an intranucleoside bond with the preceding monomer or 3'-terminal group;

R ^{2 *} and R ^{4 *} are biradicals having 1-4 groups / atoms selected from —C (R ^a R ^b ) -, —C (R ^a ) = C (R ^a ) -, —C (R ^a ) = N-, -O-, -Si (R ^a ) ₂ -, -S-, -SO ₂ -, -N (R ^a ) - and> C = Z, where Z is selected from -O-, -S- and —N (R ^a ) -, and R ^a and R ^b are each independently selected from hydrogen, optionally substituted C _1-12 alkyl, optionally substituted C _2-12 alkenyl, optionally substituted C _2-12 alkynyl , hydroxy, C _1-12 -alkoxy, C _2-12 -alkeniloksi, carboxy, C _1-12 -alkoxycarbonyl, C _1-12 -alkylcarbonyl, formyl, aryl, aryloxycarbonyl, aryloxy, arylcarbonyl, heteroaryl, heteroaryloxycarbonyl, heteroaryloxy, hetero rilkarbonila, amino, mono- and di (C _1-6 alkyl) amino, carbamoyl, mono- and di (C _1-6 -alkyl) aminocarbonyl, amino-C _1-6 -alkylaminocarbonyl, mono- and di (C _{1 -6-} alkyl) amino-C _1-6 -alkylaminocarbonyl, C _1-6 -alkylcarbonylamino, carbamido, C _1-6 -alkanoyloxy, sulfono, C _1-6 -alkylsulfonyloxy, nitro, azido, sulfanyl, C _1-6 - alkylthio, halogen, DNA intercalators, photochemically active groups, thermochemically active groups, chelating groups, reporter groups and ligands, where aryl and heteroaryl may optionally be substituted and where two heminine substituents R ^a and R ^b in optionally substituted methylene olefin (= CH ₂ );

each of the substituents R ^{1 *} , R ² , R ^{3 *} , R ⁵ R ^{5 *} , R ⁶ and R ^{6 *} present are each independently selected from hydrogen, optionally substituted C _1-12 alkyl, optionally substituted C _2-12 alkenyl, optionally substituted C _2-12 alkynyl, hydroxy, C _1-12 alkoxy, C _2-12 alkenyloxy, carboxy, C _1-12 alkoxycarbonyl, C _1-12 alkylcarbonyl, formyl, aryl, aryloxycarbonyl, aryloxy, arylcarbonyl , heteroaryl, heteroaryloxycarbonyl, heteroaryloxy, heteroarylcarbonyl, amino, mono and di (C _1-6 alkyl) amino, carbamoyl, mono and di (C _1-6 alkyl) aminocarbonyl, amino C _1-6 alkyl l-aminocarbonyl, mono- and di (C _1-6 -alkyl) amino-C _1-6 -alkylaminocarbonyl, C _1-6 -alkylcarbonylamino, carbamido, C _1-6 -alkanoyloxy, sulfono, C _1-6 -alkylsulfonyloxy, nitro, azido, sulfanyl, C _1-6 alkylthio, halogen, DNA intercalators, photochemically active groups, thermochemically active groups, chelating groups, reporter groups and ligands, where aryl and heteroaryl may optionally be substituted and where two hemin substituents together can represent oxo, thioxo, imino or optionally substituted methylene, or together they can form with irobiradikal consisting of an alkylene chain containing 1-5 carbon atoms which optionally contains inside and / or on the end of one / one or more heteroatoms / groups selected from -O-, -S- or - (NR ^N) -, where R ^{N is} selected from hydrogen and C _1-4 alkyl, and wherein two adjacent (non-heminic) substituents may represent an additional bond leading to the formation of a double bond;

R ^{N *} , if present, is selected from hydrogen and C _1-4 alkyl;

and its basic salts and acid addition salts.

2. The oligomer according to claim 1, comprising 1-10000 xylo ZNAs of the general formula I and 0-10000 nucleosides selected from natural nucleosides and nucleoside analogues, provided that the sum of the number of nucleosides and the number of xylo ZNA is at least 2, preferably at least 3, falling within an interval such as 2-15000.

3. The oligomer according to claim 2, characterized in that at least one xylo-ZNA includes a nucleotide base as a substituent B.

4. The oligomer according to claim 2, characterized in that said oligonucleotide comprises at least 7, preferably at least 9, in particular at least 11, in particular at least 13, consecutive xyl-ZNA monomers.

5. The oligomer according to claim 2, characterized in that all nucleoside monomers of the oligomer are xyl-ZNA.

6. The oligomer according to any one of claims 1 to 5, characterized in that the xyl-ZNA has / have the following formula Ia

where P, P ^* , B, X, R ^{1 *} , R ² , R ^{2 *} , R ^{3 *} , R ^{4 *} , R ⁵ and R ^{5 * are} defined in claim 1.

7. The oligomer according to any one of claims 1 to 6, in which X is selected from - (CR ⁶ R ^{6 *} ) -, —O—, —S— and —N (R ^{N *} ) -, preferably from —O—, -S- and -N (R ^{N *} ) - and in particular -O-.

8. The oligomer according to any one of claims 1 to 7, in which the biradical formed by R ^{2 *} and R ^{4 *} is selected from - (CR ^* R ^* ) _r -Y- (CR ^* R ^* ) _s -, - (CR ^* R ^* ) _r -Y- (CR ^* R ^* ) _s -Y-, -Y- (CR ^* R ^* ) _{r + s} -Y-, -Y- (CR ^* R ^* ) _r -Y- (CR ^* R ^* ) _s -, - (CR ^* R ^* ) _{r + s} -, -Y-, -YY-, where each Y is independently selected from -O-, -S-, -Si (R ^* ) ₂ -, -N (R ^* ) -,> C = O, -C (= O) -N (R ^* ) - and -N (R ^* ) -С (= O) -, each R ^{* is} independently selected from hydrogen, halogen , azido, cyano, nitro, hydroxy, mercapto, amino, mono- or di (C _1-6 -alkyl) amino, optionally substituted C _1-6 -alkoxy, optionally substituted C _1-6 -alkyl, DNA intercalators, photochemically active groups, thermochemically active groups, hel iruyuschih groups, reporter groups, and ligands, and / or two adjacent (nonheme) R ^* may together designate a double bond and each r and s = 0-4, with the proviso that the sum r + s = 1-4.

9. The oligomer of claim 8, wherein said biradical is selected from -Y-, - (CR ^* R ^* ) _{r + s} -, - (CR ^* R ^* ) _r -Y- (CR ^* R ^* ) _s - and -Y- (CR ^* R ^* ) _{r + s} -Y-, where each r and s = 0-3, provided that the sum r + s = 1-4.

10. The oligomer of claim 9, wherein said biradical is selected from —O—, —S—, —N (R ^* ) -, - (CR ^* R ^* ) _{r + s + l} -, - (CR ^* R ^* ) _r -O- (CR ^* R ^* ) _s -, - (CR ^* R ^* ) _r -S- (CR ^* R ^* ) _s -, - (CR ^* R ^* ) _r -N (R ^* ) - ( CR ^* R ^* ) _s -, -O- (CR ^* R ^* ) _{r + s} -O-, -S- (CR ^* R ^* ) _{r + s} -O-, -O- (CR ^* R ^* ) _{r + s} -S-, -N (R ^* ) - (CR ^* R ^* ) _{r + s} -O-, -O- (CR ^* R ^* ) _{r + s} -N (R ^* ) -, -S- ( CR ^* R ^* ) _{r + s} -S-, -N (R ^* ) - (CR ^* R ^* ) _{r + s} -N (R ^* ) -, -N (R ^* ) - (CR ^* R ^* ) _{r + s} -S- and -S- (CR ^* R ^* ) _{r + s} -N (R ^* ) -, where each r and s = 0-3, provided that the sum r + s = 1-4, and where X is selected from —O—, —S— and —N (R ^H ) -, and R ^H is hydrogen or C _1-4 alkyl.

11. The oligomer of claim 10, wherein X is O, R ^{2 is} selected from hydrogen, hydroxy and optionally substituted C _1-6 alkoxy, and R ^{1 *} , R ^{3 *} , R ⁵ and R ^{5 *} are hydrogen.

12. The oligomer according to claim 11, wherein said biradical is selected from —O—, - (CH ₂ ) _0-1 —O— (CH ₂ ) _1-3 -, - (CH ₂ ) _0-1 —S- ( CH ₂ ) _1-3 - and - (CH ₂ ) _0-1 -N (R ^N ) - (CH ₂ ) _1-3 -.

13. The oligomer according to claim 12, wherein said biradical is selected from —O — CH ₂ -, —S — CH ₂ -, and —N (R ^N ) —CH ₂ -.

14. The oligomer according to any one of claims 11 to 13, wherein B is selected from nucleotide bases.

15. The oligomer according to 14, characterized in that said oligomer comprises at least one xylo-ZNA, where B is selected from adenine and guanine, and at least one xylo-ZNA, where B is selected from thymine, cytosine and uracil.

16. The oligomer according to claim 8, characterized in that said biradical is - (CH ₂ ) _2-4 -.

17. The oligomer according to any one of claims 8 to 10, in which one R ^{* is} selected from hydrogen, hydroxy, optionally substituted C _1-6 alkoxy, optionally substituted C _1-6 alkyl, DNA intercalators, photochemically active groups, thermochemically active groups, chelating groups, reporter groups and ligands, and any other remaining R ^* substituents are hydrogen.

18. The oligomer according to 17, in which the R ^* group in the biradical of at least one xylo-ZNA is selected from DNA intercalators, photochemically active groups, thermochemically active groups, chelating groups, reporter groups and ligands.

19. The oligomer according to any one of claims 1 to 18, in which any intranucleoside bond in xyl-ZNA is selected from bonds consisting of 2-4, preferably 3, groups / atoms selected from -CH ₂ -, -O-, - S-, -NR ^H -,> C = O,> C = NR ^H ,> C = S, -Si (R ") ₂ -, -SO-, -S (O) ₂ -, -P (O) ₂ -, -P (O, S) -, -P (S) ₂ -, -PO (R '') -, -PO (OCH ₃ ) - and -PO (NHR ^H ) -, where R ^{H is} selected from hydrogen and C _1-4 alkyl, and R ″ is selected from C _1-6 alkyl and phenyl.

20. The oligomer according to claim 19, in which any intranucleoside bond in xyl-ZNA is selected from —CH ₂ —CH ₂ —CH ₂ -, —CH ₂ —CO — CH ₂ -, —CH ₂ —CHON — CH ₂ -, —O — CH ₂ —O—, —O — CH ₂ —CH ₂ -, —O — CH ₂ —CH =, —CH ₂ —CH ₂ —O—, —NR ^H —CH ₂ —CH ₂ -, - CH ₂ —CH ₂ —NR ^H -, —CH ₂ —NR ^H CH ₂ -, —O — CH ₂ —CH ₂ —NR ^H -, —NR ^H —CO — O—, —NR ^H —CO — NR ^H -, -NR ^H -CS-NR ^H -, -NR ^H -C - (= NR ^H ) -NR ^H -, -NR ^H -CO-CH ₂ -NR ^H -, -O-CO-O-, - O-CO-CH ₂ -O-, -O-CH ₂ -CO-O-, -CH ₂ -CO-NR ^H -, -O-CO-NR ^H -, -NR ^H -CO-CH ₂ -, —O — CH ₂ —CO — NR ^H -, —O — CH ₂ —CH ₂ —NR ^H -, —CH = N — O—, —CH ₂ —NR — O—, —CH ₂ —O — N = , -CH ₂ -O-NR ^H -, -CO-NR ^H CH ₂ -, -CH ₂ -NR ^H -O-, -CH ₂ -NR ^H -CO-, -O-NR ^H -CH ₂ -, -O-NR-, -O-CH ₂ -S-, -S-CH ₂ -O-, -CH ₂ -CH ₂ -S-, -O-CH ₂ -CH ₂ -S-, -S-CH ₂ -CH =, -S-CH ₂ -CH ₂ -, -S-CH ₂ -CH ₂ -O-, -S-CH ₂ -CH ₂ -S-, -CH ₂ -S-CH ₂ -, - CH ₂ —SO — CH ₂ - , —CH ₂ —SO ₂ —CH ₂ -, —O — SO — O—, —O — S (O) ₂ —O—, —O — S (O) ₂ —CH ₂ -, —O — S ( O) ₂ —NR ^H -, —NR ^H —S (O) ₂ —CH ₂ -, —O — S (O) ₂ —CH ₂ -, —O — P (O) ₂ —O—, —O— P (O, S) -O, -O-P (S) ₂ -O-, -SP (O) ₂ -O-, -SP (O, S) -O-, -SP (S) ₂ -O -, O-P (O) ₂ -S-, -O-P (O, S) -S-, -O-P (S) ₂ -S-, -SP (O) ₂ -S-, -SP (O, S) -S, -SP (S) ₂ -S-, -O-PO (R ") - O-, -O-PO (OCH ₃ ) -O-, -O-PO (BH ₃ ) -O, -O-PO (NHR ^N ) -O-, -O-P (O) ₂ -NR ^H -, -NR ^H -P (O) ₂ -O-, -O-P (O, NR ^H ) -O- and O-Si (R``) ₂ -O-.

21. The oligomer according to claim 20, in which any intranucleoside bond in xyl-ZNA is selected from —CH ₂ —CO — NR ^H -, —CH ₂ —NR ^H —O—, —S — CH ₂ —O—, —O -P (O) ₂ -O-, -O-P (O, S) -O-, -O-P (S) ₂ -O-, -NR ^H -P (O) ₂ -O-, -O -P (O, NR ^H ) -O-, -O-PO (R``) - O-, -O-PO (CH ₃ ) -O- and -O-PO (NHR ^N ) -O-, where R ^{H is} selected from hydrogen and C _1-4 alkyl and R ″ is selected from C _1-4 alkyl and phenyl.

22. The oligomer according to any one of claims 1 to 21, in which each of the substituents R ^{1 *} , R ² , R ^{3 *} , R ⁵ , R ^{5 *} , R ⁶ and R ^{6 *} in xyl-ZNA, if any are independently selected from hydrogen, optionally substituted C _1-6 alkyl, optionally substituted C _2-6 alkenyl, hydroxy, C _1-6 alkoxy, C _2-6 alkenyloxy, carboxy, C _1-6 alkoxycarbonyl, C _1-6- alkylcarbonyl, formyl, amino, mono- and di (C _1-6 -alkyl) amino, carbamoyl, mono- and di (C _1-6 -alkyl) aminocarbonyl, C _1-6 -alkylcarbonylamino, carbamido, azido , C _1-6 alkanoyloxy, sulfono, sulfanyl, C _1-6 alkylthio, DNA intercalators, photochemically a active groups, thermochemically active groups, chelating groups, reporter groups and ligands, as well as halogen, moreover, two hemin substituents together can form oxo, and R ^{N *} , if it is present and is not included in the biradical, they are selected from hydrogen and C _1-4 alkyl.

23. The oligomer according to any one of claims 1 to 22, in which X is selected from —O—, —S— and —NR ^{N *} , and each of the substituents R ^{1 *} , R ² , R ^{3 *} , R ⁵ R ^{5 *} , R ⁶ and R ^{6 *} in xyl-ZNA, if present, is hydrogen.

24. The oligomer according to any one of claims 1 to 23, in which P denotes a 5'-terminal group selected from hydrogen, hydroxy, optionally substituted C _1-6 alkyl, optionally substituted C _1-6 alkoxy, optionally substituted C _{1 -6-} alkylcarbonyloxy, optionally substituted aryloxy, monophosphate, diphosphate, triphosphate and -W-A ', where W is selected from -O-, -S- and -N (R ^H ) -, where R ^{H is} selected from hydrogen and C _{1 -6-} alkyl, and where A 'is selected from DNA intercalators, photochemically active groups, thermochemically active groups, chelating groups, reporter groups and ligands.

25. The oligomer according to any one of claims 1 to 24, in which P * denotes a 3'-terminal group selected from hydrogen, hydroxy, optionally substituted C _1-6 alkoxy, optionally substituted C _1-6 alkylcarbonyloxy, optionally substituted aryloxy and -W-A ', where W is selected from -O-, -S- and -N (R ^H ) -, where R ^{H is} selected from hydrogen and C _1-6 alkyl, and where A' is selected from DNA intercalators, photochemically active groups, thermochemically active groups, chelating groups, reporter groups and ligands.

26. The oligomer according to any one of claims 1 to 25, corresponding to the following formula V:

where q = 1-50;

each of n (0), ..., n (q) is independently 0-10000;

each of m (1), ..., m (q) is independently 1-10000;

provided that the sum of n (0), ..., n (q) and m (1), ..., m (q) is 2-15000;

G represents a 5'-terminal group;

each Nu independently represents a nucleoside selected from natural nucleosides and nucleoside analogues;

each xylo-ZNA independently denotes a nucleoside analogue;

each L independently represents an intranucleoside linkage between two groups selected from Nu and xyl-ZNA, or L together with G * represents a 3’-terminal group; and each xylo-ZNA-L independently denotes a nucleoside analogue of the general formula I.

27. Nucleoside analogue of xylo-ZNA of General formula II

where Deputy B is selected from nucleotide bases, DNA intercalators, photochemically active groups, thermochemically active groups, chelating groups, reporter groups and ligands;

X is selected from —O—, —S—, —M (R ^{N *} ) - and —C (R ⁶ R ⁶ *) -;

each of Q and Q ^{* is} independently selected from hydrogen, azido, halogen, cyano, nitro, hydroxy, Prot-O-, Act-O-, mercapto, Prot-S-, Act-S-, C _1-6 -alkylthio, amino, Prot-N (R ^H ) -, Act-N (R ^H ) -, mono- or di (C _1-6 -alkyl) amino, optionally substituted C _1-6 alkoxy, optionally substituted C _1-6 - alkyl, optionally substituted C _2-6 alkenyl, optionally substituted C _2-6 alkenyloxy, optionally substituted C _1-6 alkynyl, optionally substituted C _2-6 alkynyloxy, monophosphate, diphosphate, triphosphate, DNA intercalators, photochemically active groups thermochemically active gru pp, chelating groups, reporter groups, ligands, carboxy, sulfono, hydroxymethyl, Prot-O-CH ₂ -, Act-O-CH ₂ -, aminomethyl, Prot-N (R ^H ) -CH ₂ -, Act-N ( R ^H ) —CH ₂ -, carboxymethyl, sulfonomethyl, where Prot is a protecting group for —OH, —SH and —NH (R ^H ) - respectively, Act is an activating group for —OH, —SH and —NH (R ^H ), respectively and R ^{H is} selected from hydrogen and C _1-6 alkyl;

R ^{2 *} and R ^{4 *} together denote a biradical selected from -O-, - (CR ^* R ^* ) _{r + s + l} -, - (CR ^* R ^* ) _r -O- (CR ^* R ^* ) _s - , - (CR ^* R ^* ) _r -S- (CR ^* R ^* ) _s -, - (CR ^* R ^* ) _r -N (R ^* ) - (CR ^* R ^* ) _s -, -O- (CR ^* R ^* ) _{r + s} -O-, -S- (CR ^* R ^* ) _{r + s} -O-, -O- (CR ^* R ^* ) _{r + s} -S-, -N (R ^* ) - (CR ^* R ^* ) _{r + s} -O-, -O- (CR ^* R ^* ) _{r + s} -N (R ^* ) -, -S- (CR ^* R ^* ) _{r + s} -S-, - N (R ^* ) - (CR ^* R ^* ) _{r + s} -N (R ^* ) -, -N (R ^* ) - (CR ^* R ^* ) _{r + s} -S- and -S- (CR ^* R ^* ) _{r + s} -N ( ^* R ^* ) -,

where each R ^* is independently selected from hydrogen, halogen, azido, cyano, nitro, hydroxy, mercapto, amino, mono- or di (C _1-6 alkyl) amino, optionally substituted C _1-6 alkoxy, optionally substituted C _{1 -6} -alkyl, DNA intercalators, photochemically active groups, thermochemically active groups, chelating groups, reporter groups, and ligands, and / or two adjacent (non-hemine) R ^* can together denote a double bond and each r and s = 0-3, provided that the sum r + s = 1-4;

each of the substituents present R ^{1 *} , R ² , R ^{3 *} , R ⁵ R ^{5 *} , R ⁶ and R ^{6 * are} independently selected from hydrogen, optionally substituted C _2-12 alkyl, optionally substituted C _2-12 alkenyl, optionally substituted C _2-12 alkynyl, hydroxy, C _1-12 alkoxy, C _2-12 alkenyloxy, carboxy, C _1-12 alkoxycarbonyl, C _1-12 alkylcarbonyl, formyl, aryl, aryloxycarbonyl, aryloxy, arylcarbonyl , heteroaryl, heteroaryloxycarbonyl, heteroaryloxy, heteroarylcarbonyl, amino, mono- and di (C _1-6 alkyl) amino, carbamoyl, mono- and di (C _1-6 -alkyl) aminocarbonyl, amino-C _1-6 -a kilaminokarbonila, mono- and di (C _1-6 -alkyl) amino-C _1-6 -alkylaminocarbonyl, C _1-6 -alkilkarbonilamino, carbamido, C _1-6 -alkanoyloxy, sulphono, C _1-6 -alkilsulfoniloksi, nitro, azido, sulfanyl, C _1-6 alkylthio, halogen, DNA intercalators, photochemically active groups, thermochemically active groups, chelating groups, reporter groups and ligands, where aryl and heteroaryl may optionally be substituted and where two hemin substituents together may represent oxo, thioxo, imino or optionally substituted methylene, or together they can form a spiro-biradical consisting of an alkylene chain containing 1-5 carbon atoms, which optionally contains inside and / or at the end one / one or more heteroatoms / groups selected from —O—, —S— or - (NR ^N ) - where R ^{N is} selected from hydrogen and C _1-4 alkyl and where two adjacent (non-heminic) substituents may indicate an additional bond leading to the formation of a double bond; and R ^{N *} , if present and not included in the biradical, is selected from hydrogen and C _1-4 alkyl;

and its basic salts and acid addition salts;

and provided that any chemical group (including any nucleotide base) that is reactive under the conditions prevailing in the process of oligonucleotide synthesis is an optionally protected functional group.

28. Xylo-ZNA according to item 27, in which group B is selected from nucleotide bases and nucleotide bases with a protected functional group.

29. Xyl-ZNA according to any one of claims 27 to 28, wherein X is selected from —O—, —S— and —N (R ^{N *} ) -.

30. Xyl-ZNA according to any one of paragraphs.27-29, in which each of the substituents R ^{1 *} , R ² , R ^{3 *} , R ⁵ , R ^{5 *} , R ⁶ and R ^{6 *} , if any, independently selected from hydrogen, optionally substituted C _1-6 alkyl, optionally substituted C _2-6 alkenyl, hydroxy, C _1-6 alkoxy, C _2-6 alkenyloxy, carboxy, C _1-6 alkoxycarbonyl, C _{1- 6-} alkylcarbonyl, formyl, amino, mono- and di (C _1-6 -alkyl) amino, carbamoyl, mono- and di (C _1-6 -alkyl) aminocarbonyl, C _1-6 -alkylcarbonylamino, carbamido, azido, C _1-6 alkanoyloxy, sulfonyl, sulfanyl, C _1-6 -alkylthio, DNA intercalators, photochemically active RUPP, thermochemically active groups, chelating groups, reporter groups, ligands, and halogen, wherein geminovyh two substituents together may form an oxo, and R ^{N *,} in the case if it is available and not part of the biradical is selected from hydrogen and C _{1- 4-} alkyl, provided that any group of hydroxy, amino, mono (C _1-6 -alkyl) amino, sulfanyl and carboxy is optionally protected.

31. Xyl-ZNA according to any one of paragraphs.27-30, in which each of the substituents R ^{1 *} , R ² , R ^{3 *} , R ⁵ , R ^{5 *} , R ⁶ and R ^{6 *} , if any, means hydrogen.

32. Xyl-ZNA according to any one of claims 27-31, wherein Q is independently selected from hydrogen, azido, halogen, cyano, nitro, hydroxy, Prot-O-, mercapto, Prot-S-, C _1-6 -alkylthio , amino, Prot-N (R ^H ) -, mono- or di (C _1-6 alkyl) amino, optionally substituted C _1-6 alkoxy, optionally substituted C _1-6 alkyl, optionally substituted C _2-6 alkenyl, optionally substituted C _2-6 alkenyloxy, optionally substituted C _2-6 alkynyl, optionally substituted C _2-6 alkynyloxy, monophosphate, diphosphate, triphosphate, DNA intercalators, photochemically active groups, thermochemically act large groups, chelating groups, reporter groups, ligands, carboxy, sulfono, hydroxymethyl, Prot-O-CH ₂ -, aminomethyl, Prot-N (R ^H ) -CH ₂ -, carboxymethyl, sulfonomethyl, where Prot denotes a protective group for - OH, —SH and —NH (R ^H ) -, respectively, and R ^H are selected from hydrogen and C _1-6 alkyl; and Q * are selected from hydrogen, azido, halogen, cyano, nitro, hydroxy, Act-O-, mercapto, Act-S-, C _1-6 -alkylthio, amino, Act-N (R ^H ) -, mono- or di (C _1-6 alkyl) amino, optionally substituted C _1-6 alkoxy, optionally substituted C _1-6 alkyl, optionally substituted C _2-6 alkenyl, optionally substituted C _2-6 alkenyloxy, optionally substituted C _2-6 -alkynyl, optionally substituted C _2-6 -alkiniloksi, DNA intercalators, photochemically active groups, thermochemically active groups, chelating groups, reporter groups, ligands, carboxy, sulphono, where Act boznachaet activating group for -OH, -SH and -NH (R ^H), respectively, and R ^H is selected from hydrogen and C _1-6 -alkyl.

33. Xylo-ZNA according to any one of paragraphs.27-32, in which B is in the β-configuration.

34. The xylo-ZNA according to claim 33, wherein X is O, R ^{2 is} selected from hydrogen, hydroxy and optionally substituted C _1-6 alkoxy, and R ^{1 *} , R ³ , R ⁵ and R ^{5 *} are hydrogen.

35. Xyl-ZNA according to claims 27-34, wherein the biradical is selected from -O-, - (CH ₂ ) _0-1 -O- (CH ₂ ) _1-3 -, - (CH ₂ ) _0-1 - S- (CH ₂ ) _1-3 - and - (CH ₂ ) _0-1 -N (R ^N ) - (CH ₂ ) _1-3 -.

36. The xylo-ZNA according to claim 35, wherein said biradical is selected from —O — CH ₂ -, —S — CH ₂ -, and —N (R ^N ) —CH ₂ -.

37. Xylo-ZNA according to any one of claims 34-36, wherein B is selected from nucleotide bases.

38. Xylo-ZNK by 37, in which B is selected from adenine, guanine, thymine, cytosine and uracil.

39. The xylo-ZNA of claim 38, wherein the biradical is - (CH ₂ ) _2-4 -, preferably - (CH ₂ ) ₂ -.

40. Xyl-ZNA according to any one of claims 34-39, wherein one R ^{* is} selected from hydrogen, hydroxy, optionally substituted C _1-6 alkoxy, optionally substituted C _1-6 alkyl, DNA intercalators, photochemically active groups, thermochemically active groups, chelating groups, reporter groups and ligands, and any other remaining R ^* substituents are hydrogen.

41. Xyl-ZNA according to any one of paragraphs.27-40 to obtain a xyl-ZNA-modified oligonucleotide (oligomer) according to any one of claims 1-34.

42. Xylo-ZNA according to paragraph 41, wherein the inclusion of xylo-ZNA modulates the ability of the oligonucleotide to act as a substrate for enzymes active against nucleic acids.

43. Xylo-ZNA according to any one of paragraphs.27-40 to obtain a conjugate of a xyl-ZNA-modified oligonucleotide and a compound selected from proteins, amplicons, enzymes, polysaccharides, antibodies, haptens, peptides and PNA.

44. The conjugate of a xyl-ZNA-modified oligonucleotide (oligomer), as defined in any one of claims 1 to 26, and a compound selected from proteins, amplicons, enzymes, polysaccharides, antibodies, haptens, peptides and PNAs.

45. Xylo-ZNA according to any one of paragraphs.27-40 for use as a substrate for enzymes active against nucleic acids.

46. Xylo-ZNA according to item 45, wherein the substituent Q in formula II according to item 31 denotes triphosphate.

47. Xylo-ZNA according to item 45, wherein xylo-ZNA is used as a substrate for DNA and RNA polymerases.

48. Xylo-ZNA according to any one of paragraphs.27-40 for use as a medicine,

49. Xylo-ZNA according to any one of paragraphs.27-40 for diagnostic purposes.

50. One or more xylo-LNAs according to any one of claims 27-40 for use in the construction of a solid surface to which LNA-modified oligonucleotides with different sequences are attached.

51. The xyl-ZNA-modified oligomer (ribozyme) according to any one of claims 1 to 26 for use in sequence-specific cleavage of target nucleic acids.

52. The xyl-ZNA-modified oligonucleotide (oligomer) according to any one of claims 1 to 26 for use in therapy, for example, in antisense, antigenic, or gene-activating therapy.

53. The xyl-ZNA-modified oligonucleotide (oligomer) according to paragraph 52, wherein the ZNA-modified oligonucleotide mobilizes RNazuH.

54. The xyl-ZNA-modified oligonucleotide (oligomer) according to any one of claims 1 to 26 in a complex of more than one of these oligonucleotides for use in therapy, for example, in antisense, antigenic, or gene-activating therapy.

55. Xyl-ZNA-modified oligonucleotide (oligomer) according to any one of claims 1 to 26 for use in therapy as an aptamer.

56. The xyl-ZNA-modified oligonucleotide (oligomer) according to any one of claims 1 to 26 for use in diagnostics, for example, for isolation, purification, amplification, detection, identification, quantification or capture of natural or synthetic nucleic acids.

57. The xyl-ZNA-modified oligonucleotide (oligomer) of claim 56, wherein said oligonucleotide comprises a photochemically active group, a thermochemically active group, a chelating group, a reporter group or a ligand, each of which facilitates direct or indirect detection of the oligonucleotide or immobilization of the solid oligonucleotide the substrate.

58. The xyl-ZNA-modified oligonucleotide (oligomer) of claim 57, wherein said photochemically active group, thermochemically active group, chelating group, reporter group or ligand includes a spacer (K), said spacer comprising a chemically cleavable group.

59. The xyl-ZNA-modified oligonucleotide (oligomer) according to § 58, wherein said photochemically active group, thermochemically active group, chelating group, reporter group or ligand is attached via a diradical (ie, as R ^* ) of at least one ZNA in the oligonucleotide.

60. The xyl-ZNA-modified oligonucleotide (oligomer) according to § 58 for the capture and detection of natural or synthetic double-stranded or single-stranded nucleic acids, such as RNA or DNA.

61. The xyl-ZNA-modified oligonucleotide (oligomer) according to clause 57 for the purification of natural double-stranded or single-stranded nucleic acids, such as RNA or DNA.

62. The xyl-ZNA-modified oligonucleotide (oligomer) of claim 57 for use as a sample in in situ hybridization, Southern hybridization, dot blot hybridization, reversible dot blot hybridization, or Northern hybridization.

63. The xyl-ZNA-modified oligonucleotide (oligomer) according to any one of claims 1 to 26 for use as an aptamer in molecular diagnostics.

64. The xyl-ZNA-modified oligonucleotide (oligomer) according to any one of claims 1 to 26 for use as an aptamer in RNA-mediated catalytic processes.

65. The xyl-ZNA-modified oligonucleotide (oligomer) according to any one of claims 1 to 26 for use as an aptamer for the specific binding of antibiotics, drugs, amino acids, peptides, structural proteins, protein receptors, enzyme proteins, saccharides, polysaccharides, biological cofactors, nucleic acids or triphosphates.

66. The xyl-ZNA-modified oligonucleotide (oligomer) according to any one of claims 1 to 26 for use as an aptamer in the separation of enantiomers from racemic mixtures by stereospecific binding.

67. Xyl-ZNA-modified oligonucleotide (oligomer) according to any one of claims 1 to 26 for labeling cells.

68. The xyl-ZNA-modified oligonucleotide (oligomer) of claim 67, wherein said label allows cells to be separated from unlabeled cells.

69. The xyl-ZNA-modified oligonucleotide (oligomer) according to any one of claims 1 to 26 for hybridizing non-coding protein to cellular RNAs, such as tRNA, rRNA, snRNA and mcRNA, in vivo or in vitro.

70. The xyl-ZNA-modified oligonucleotide (oligomer) according to any one of claims 1 to 26 for constructing an oligonucleotide comprising a fluorophore and a quencher located so that the hybridization state of the oligonucleotide can be distinguished from the unbound state of the oligonucleotide by amplifying the fluorescent signal from the probe.

71. The xyl-ZNA-modified oligonucleotide (oligomer) according to any one of claims 1 to 26 for the construction of Takman probes (Taqman probes) or molecular "beacons" (Molecular Beacons).

72. A kit intended for isolation, purification, amplification, detection, identification, quantification or capture of natural or synthetic nucleic acids, characterized in that the kit includes a reaction base and one or more xyl-ZNA-modified oligonucleotides (oligomers) according to any one of claims 1 to 26.

73. The kit of claim 72, wherein said xyl-ZNA-modified oligonucleotides are immobilized on said reaction basis.

74. A kit intended for isolation, purification, amplification, detection, identification, quantification or capture of natural or synthetic nucleic acids, characterized in that the kit includes a reaction base and one or more xylo-ZNA according to any one of paragraphs.27- 40.

75. The kit of claim 74, wherein said xyl-ZNA is immobilized on said reaction base.