RU2000109306A - BI- AND TRICYCLIC ANALOGUES OF NUCLEOSIDES, NUCLEOTIDES AND OLIGONUCLEOTIDES - Google Patents

Claims (140)

1. The oligomer (hereinafter referred to as "LNA-modified oligonucleotide"), comprising at least one nucleoside analogue (hereinafter referred to as "LNA") of General formula I

where X is selected from —O—, —S—, —N (R ^{N *} ) -, —C (R ⁶ R ^{6 *} ) -, —OC (R ⁷ R ^{7 *} ) -, —C (R ⁶ R ^{6 *} ) -O-, -SC (R ⁷ R ^{7 *} ) -, -C (R ⁶ R ^{6 *} ) -S-, -N (R ^{N *} ) -C (R ⁷ R ^{7 *} ) -, -C (R ⁶ R ^{6 *} ) —N (R ^{N *} ) - and —C (R ⁶ R ^{6 *} ) —C (R ⁷ R ^{7 *} ) -;
B is selected from hydrogen, hydroxyl, an optionally substituted C _1-4 alkoxy group, an optionally substituted C _1-4 alkyl, an optionally substituted C _1-4 acyloxy group, nucleotide bases, DNA intercalating agents, photochemically active groups, thermochemically active groups, chelating groups, reporter groups and ligands;
P denotes the position of the radical for the formation of the internucleoside "bridge" with the next monomer or 5'-terminal group, and such an internucleotide bond or 5'-terminal group optionally includes a substituent R ⁵ ;
one of the substituents R ² , R ^{2 *} , R ³ and R ^{3 *} is a P ^* group that forms an internucleoside "bridge" with the preceding monomer or a 3'-terminal group;
one or two pairs of non-heminal substituents are selected from the available substituents R ^{1 *} , R ^{4 *} , R ⁵ , R ^{5 *} , R ⁶ , R ^{6 *} , R ⁷ , R ^{7 *} , R ^{N *} , and each of the substituents R ² , R ^{2 *} , R ³ and R ^{3 *} , not representing P ^* , denote a biradical consisting of 1-8 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 ³ ) - and> C = Z,
where Z is selected from —O—, —S— and —N (R ^a ) -, a R ^a and R ^{b are} independently selected from hydrogen, optionally substituted C _1-12 alkyl, optionally substituted C _2-12 - alkenyl, C _2-12 alkynyl, optionally substituted hydroxyl, 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 groups, heteroarylcarbonyl, amino groups, mono and di (C _1-6 alkyl) amino groups, 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 groups, sulfonic groups, C _1-6 alkylsulfonyloxy groups, nitro groups, azido groups, sulfanyl, C _1-6 alkylthio groups, halogen, DNA intercalating groups, photochemically active groups, thermochemically active groups, chelating groups, reporter groups and ligands, where aryl and heteroaryl may be optionally substituted and where two geminal substituent R ^a and R ^b together could t form an optionally substituted methylene (= _CH2), and where two geminal or negeminalnyh substituents selected from R ^a, R ^b and each of the substituents R ^{1 *,} R ^2, R ^{2 *,} R ^3, R ^{3 *,} R ^{4 *} , R ⁵ , R ^{5 *} , R ⁶ and R ^{6 *} , R ⁷ and R ^{7 *} , which are present and are not involved in P, P ^* or the diradical (diradicals), together can form a linked diradical selected from the diradicals of the same type as defined above;
the specified pair (s) of non-heminal substituents thereby form a mono- or bicyclic structure together with (i) the atoms to which the non-heminal substituents are attached, and (ii) with any intermediate atoms; and
each of the substituents R ^{1 *} , R ² , R ^{2 *} , R ³ , R ^{4 *} , R ⁵ , R ^{5 *} , R ⁶ and R ^{6 *} , R ⁷ and R ^{7 *} , which are present and not involved in P, P ^* or biradical (s) are independently selected from hydrogen, optionally substituted C _1-12 alkyl, optionally substituted C _2-12 alkenyl, optionally substituted C _2-12 alkynyl, optionally substituted hydroxyl, C _1-12 alkoxy , C _2-12 alkenyloxy groups, carboxy groups, C _1-12 alkoxycarbonyl, C _1-12 alkylcarbonyl, formyl, aryl, aryloxycarbonyl, aryloxy group, arylcarbonyl, heteroaryl, heteroaryloxycarbonyl, heter oaryloxy groups, heteroarylcarbonyl, amino groups, mono and di (C _1-6 alkyl) amino groups, 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 groups, carbamido, C _1-6 alkanoyloxy groups, sulfonic groups, C _1-6 alkylsulfonyloxy groups, nitro groups, azido groups, sulfanyl, C _1-6 alkylthio groups, halogen, DNA intercalating groups, photochemically active groups, thermochemically active groups, chelating groups, reporter groups and ligands, g dearyl and heteroaryl can be optionally substituted and where two geminal substituents together can define an oxo group, a thioxo group, an imino group or an optionally substituted methylene, or together they can form a spiro bio radical including a 1-5 carbon alkylene chain which is optionally interrupted and (or) terminated by one or more heteroatoms / groups selected from -O-, -S- and - (NR ^N) -, where R ^N is selected from hydrogen and C _1-4 -alkyl, and where two adjacent (negeminalnyh) substituents may designate an additional double with ide; and R ^{N *} , when present and not included in the diradical, is selected from hydrogen and C _1-4 alkyl;
and their basic salts and acid addition salts; provided that (i) R ² and R ³ together do not represent a biradical selected from -O-CH ₂ -CH ₂ - and -O-CH ₂ -CH ₂ -CH ₂ - where the LNA is a bicyclic nucleoside analogue; (ii) R ³ and R ⁵ together do not denote a diradical selected from —CH ₂ —CH ₂ - and —O — CH ₂ -, where LNA is a bicyclic nucleoside analogue; (iii) R ³ , R ⁵ and R ^{5 *} together do not denote the triradical —CH ₂ —CH (-) - CH ₂ -, where LNA is a tricyclic nucleoside analogue; (iv) R ^{1 *} and R ^{6 *} together do not denote the diradical —CH ₂ -, where LNA is a bicyclic nucleoside analogue; and (v) R ^{4 *} and R ^{6 *} together do not denote the diradical —CH ₂ -, where LNA is a bicyclic nucleoside analogue. 2. The oligomer according to claim 1, despite the fact that one or two pairs of non-heminal substituents comprising one or two biradicals, respectively, are selected from the substituents R ^{1 *} , R ^{4 *} , R ⁶ , R ^{6 *} , R ⁷ , R ^{7 *} , R ^{N *} , and each of the substituents R ² , R ^{2 *} , R ³ and R ^{3 *} do not denote P ^* .  3. The oligomer according to claim 1 or 2, comprising 1-10000 LNA of the general formula I and 0-10000 nucleosides selected from natural nucleosides and nucleoside analogues, provided that the sum of the amounts of nucleosides and LNA is at least 2, preferably at least 3, as, for example, in the range of 2-15000.  4. The oligomer according to claim 3, despite the fact that at least one LNA includes a nucleotide base as a substituent B. 5. The oligomer according to any one of paragraphs. 1-4, despite the fact that one of the substituents R ³ and R ^{3 *} forms P ^* . 6. The oligomer according to any one of paragraphs. 1-5, despite the fact that LNA is characterized by the following formula Ia

despite the fact that P, P ^* , B, X, R ^{1 *} , R ² , R ^{2 *} , R ³ , R ^{4 *} , R ⁵ and R ^{5 * are} defined in paragraphs. 1-5. 7. The oligomer of claim 6, wherein R ^{3 *} is P ^* .  8. The oligomer according to any one of paragraphs. 1-7, including one biradical formed by a pair of (two) non-heminal substituents. 9. The oligomer according to any one of paragraphs. 1-8, while X is selected from —C (R ⁶ R ^{6 *} ) -, —O—, —S—, —N (R ^{N *} ) -, preferably from —O—, —S— and - N (R ^{N *} ) -, in particular -O-. 10. The oligomer according to any one of paragraphs. 1-9, despite the fact that the biradical (s) are denoted by a pair (s) of non-heminal substituents 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) -, where each R ^{* is} independently selected from hydrogen, halogen, azido group, cyano group, nitro group, hydroxyl, mercapto group, amino group, mono - or di (C _1-6 -alkyl) amino group, optionally substituted with C _1-6 - alkoxy groups, optionally substituted C _1-6 alkyl, DNA intercalating groups, photochemically active groups, thermochemically active groups, chelating groups, reporter groups and ligands, and (or) two adjacent (non-heminal n) R ^* may denote a double bond; and each of r and s is 0-4 provided that the sum of r + s is 1-5. 11. The oligomer according to claim 10, despite the fact that each biradical is independently selected from -Y-, - (CR ^* R ^* ) _{r + s} -, - (CR ^* R ^* ) _r -Y- (CR ^* R ^* ) _s - and -Y- (CR ^* R ^* ) _{r + s} -Y-, while each of r and s is 0-3, provided that the sum r + s is 1-4. 12. The oligomer according to claim 11, despite the fact that
(i) R ^{2 *} and R ^{4 *} together denote a biradical selected from -Y-, - (CR ^* R ^* ) _{r + s + 1} -, - (CR ^* R ^* ) _r -Y- (CR ^* R ^* ) _s - and -H- (CR ^* R ^* ) _{r + s} -Y-;
(ii) R ² and R ³ together denote a biradical selected from -Y-, - (CR ^* R ^* ) _{r + s} -, - (CR ^* R ^* ) _r -Y- (CR ^* R ^* ) _s - and -Y- (CR ^* R ^* ) _{r + s} -Y-;
(iii) R ^{2 *} and R ³ together denote a biradical selected from -Y-, - (CR ^* R ^* ) _{r + s} -, - (CR ^* R ^* ) _r -Y- (CR ^* R ^* ) _s - and -Y- (CR ^* R ^* ) _{r + s} -Y-;
(iv) R ³ and R ^{4 *} together denote a biradical selected from -Y-, - (CR ^* R ^* ) _{r + s} -, - (CR ^* R ^* ) _r -Y- (CR ^* R ^* ) _s - and -Y- (CR ^* R ^* ) _{r + s} -Y-;
(v) R ³ and R ⁵ simultaneously mean a biradical selected from - (CR ^* R ^* ) _r -O- (CR ^* R ^* ) _s -, - (CR ^* R ^* ) _r -S- (CH ^* R ^* ) _s - and - (CR ^* R ^* ) _r -;
(vi) R ^{1 *} and R ^{4 *} simultaneously mean a biradical selected from - (CR ^* R ^* ) _r -O- (CR ^* R ^* ) _s -, - (CR ^* R ^* ) _r -S- (CR ^* R ^* ) _s - and - (CR ^* R ^* ) _r -; (vii) R ^{1 *} and R ^{2 *} together denote a biradical selected from -Y-, - (CR ^* R ^* ) _{r + s} -, - (CR ^* R ^* ) _r -Y- (CR ^* R ^* ) _s - and -Y- (CR ^* R ^* ) _{r + s} -Y-;
despite the fact that each r and s is 0-3 provided that the sum r + s is 1-4, Y is as defined above, and Y 'is selected from -NR ^* -C (= O) - and -C (= O) -NR ^* -. 13. The oligomer of claim 12, wherein one of the following criteria applies to at least one LNA (i) R ^{2 *} and R ^{4 *} together represent a diradical selected from —O—, —S—, —N (R ^* ) -, - (CR ^* R ^* ) _{r + s + 1} -, - (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 ^* ); (ii) R ² and R ³ together denote a biradical selected from (iii) R ² and R ³ together denote a biradical selected from —O—, - (CR ^* R ^* ) _{r + s} -, - (CR ^* R ^* ) _r -O- (CR ^* R ^* ) _s -, - (CR ^* R ^* ) _r -S- (CR ^* R ^* ) _s - and - (CR ^* R ^* ) _r -N (R ^* ) - ( CR ^* R ^* ) _s -; -O-, - (CR ^* R ^* ) _{r + s} -, - (CR ^* R ^* ) _r -O- (CR ^* R ^* ) _s -,
- (CR ^* R ^* ) _r -S- (CR ^* R ^* ) _s -b - (CR ^* R ^* ) _r -N (R ^* ) - (CR ^* R ^* ) _s -; (iv) R ³ and R ^{4 *} together denote a biradical selected from - (CR ^* R ^* ) _r -O- (CR ^* R ^* ) _s -,
- (CR ^* R ^* ) _r -S- (CR ^* R ^* ) _s - and - (CR ^* R ^* ) _r -N (R ^* ) - (CR ^* R ^* ) _s -; (v) R ³ and R ⁵ together denote a biradical selected from - (CR ^* R ^* ) _r -O- (CR ^* R ^* ) _s -, - (CR ^* R ^* ) _r -S- (CR ^* R ^* ) _s - and - (CR ^* R ^* ) _r -N (R ^* ) - (CR ^* R ^* ) _s -; (vi) R ^{1 *} and R ^{4 *} together denote a biradical selected from - (CR ^* R ^* ) _r -O- (CR ^* R ^* ) _s -, - (CR ^* R ^* ) _r -S- (CR ^* R ^* ) _s - and - (CR ^* R ^* ) _r -N (R ^* ) - (CR ^* R ^* ) _s -; (vii) R ^{1 *} and R ^{2 *} together denote a biradical selected from - (CR ^* R ^* ) _r -O- (CR ^* R ^* ) _s -, - (CR ^* R ^* ) _r -S- (CR ^* R ^* ) _s - and - (CR ^* R ^* ) _r -N (R ^* ) - (CR ^* R ^* ) _s -; despite the fact that each r and s is 0-3, provided that the sum r + s is 1-4, and where X is selected from -O-, -S-, and -N (R ^H ) -, where R ^H denotes hydrogen or C _1-4 alkyl. 14. The oligomer of claim 13, wherein R ^{3 *} forms P ^* . 15. The oligomer according to claim 14, while R ^{2 *} and R ^{4 *} together represent a biradical. 16. The oligomer of claim 15, wherein X is O, R ^{2 is} selected from hydrogen, hydroxyl, and an optionally substituted C _1-6 alkoxy group, and R ^{1 *} , R ³ , R ^5, and R ^{5 *} are hydrogen. 17. The oligomer of claim 16, 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 -. 18. The oligomer of claim 17, wherein the biradical is selected from —O — CH ₂ -, —S — CH ₂ -, and —N (R ^N ) —CH ₂ .  19. The oligomer according to any one of paragraphs. 15-18, while Deputy B is selected from nucleotide bases.  20. The oligomer according to claim 19, while such an oligomer includes at least one LNA, while B is selected from adenine and guanine, and at least one LNA, while B is selected from thymine, cytosine and uracil. 21. The oligomer of claim 16, wherein the biradical is - (CH ₂ ) _2-4 -. 22. The oligomer of claim 14, wherein R ² and R ³ together represent a diradical. 23. The oligomer of claim 22, wherein X is O, R ^{2 * is} selected from hydrogen, hydroxyl and an optionally substituted C _1-6 alkoxy group, and R ^{1 *} , R ^{4 *} , R ⁵ and R ^{5 *} are hydrogen. 24. The oligomer of claim 23, wherein the biradical is - (CH ₂ ) _0-1 —O— (CH ₂ ) _1-3 -. 25. The oligomer of claim 23, wherein the biradical is - (CH ₂ ) _1-4 -. 26. The oligomer according to any one of paragraphs. 14-25, while one of R ^{* is} selected from hydrogen, hydroxyl, an optionally substituted C _1-6 alkoxy group, an optionally substituted C _1-6 alkyl group, DNA intercalating groups, photochemically active groups, thermochemically active groups, chelating groups, reporter groups and ligands, and all other R ^* substituents are hydrogen. 27. The oligomer according to any one of paragraphs. 14-26, while the R ^* group of the biradical of at least one LNA is selected from DNA intercalating groups, photochemically active groups, thermochemically active groups, chelating groups, reporter groups, and ligands.  28. The oligomer according to any one of paragraphs. 14-27, despite the fact that the LNA is characterized (characterized) by the General formula Ia. 29. The oligomer according to claim 1 of the general formula Ia

while X is represented by —O—; B is selected from nucleotide bases, DNA intercalating groups, photochemically active groups, thermochemically active groups, chelating groups, reporter groups and ligands; P denotes the position of the radical for the formation of an internucleoside "bridge" followed by a monomer or a 5'-terminal group, while such an internucleoside "bridge" or a 5'-terminal group optionally includes a substituent R ⁵ ; R ^{3 *} is represented by the group P ^* , which forms the internucleoside "bridge" with the preceding monomer or 3'-terminal group; R ^{2 *} and R ^{4 *} together denote a biradical selected from -O-, -S-, -N (R ^* ) -, - (CR ^* R ^* ) _{r + s + 1} -, - (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 group, cyano group, nitro group, hydroxyl, mercapto group, amino group, mono or Li (C _1-6 alkyl) amino group, optionally substituted C _1-6 alkoxy groups, optionally substituted C _1-6 alkyl, DNA intercalating groups, photochemically active groups, thermochemically active groups, chelating groups, reporter groups and ligands, and (or) two adjacent (non-heminal) R ^* can together form a double bond, and each r and s is 0-3 provided that the sum r + s is 1-4; each of the substituents R ^{1 *} , R ² , R ³ , R ⁵ and R ^{5 * is} independently selected from hydrogen, optionally substituted C _1-6 alkyl, optionally substituted C _2-6 alkenyl, hydroxyl, C _1-6 alkoxy , C _2-6 alkenyloxy groups, carboxyl, C _1-6 alkoxycarbonyl, C _1-6 alkylcarbonyl, formyl, amino groups, mono and di (C _1-6 alkyl) amino groups, carbamoyl, mono and di (C _1-6 alkyl) aminocarbonyl, C _1-6 -alkilkarbonilaminogruppy, carbamido, azido, C _1-6 -alkanoiloksigruppy, a sulfonic group, sulfanyl, C _1-6 alkylthio, DNA-intercalating groups photochemically acti explicit groups, thermochemically active groups, chelating groups, reporter groups and ligands and halogen, where two geminal substituents together can form an oxo group; and their basic salts and acid addition salts. 30. The oligomer of claim 29, wherein one of R ^{* is} selected from hydrogen, hydroxyl, an optionally substituted C _1-6 alkoxy group, an optionally substituted C _1-6 alkyl, DNA intercalating groups, photochemically active groups, thermochemically active groups, chelating groups, reporter groups and ligands, and all other R ^* substituents are hydrogen. 31. The oligomer according to any one of paragraphs. 29-30, while the biradical is selected from —O—, - (CH ₂ ) _0-1 —O— (CH ₂ ) _1-3 -, - (CH ₂ ) _0-1 —S- (CH ₂ ) _1-3 , - (CH ₂ ) _0-1 -N (R ^N ) - (CH ₂ ) _1-3 - and - (CH ₂ ) _2-4 -. 32. The oligomer of claim 31, wherein the biradical is selected from —O — CH ₂ -, —S — CH ₂ -, and —N (R ^N ) —CH ₂ .  33. The oligomer according to any one of paragraphs. 29-32, while Deputy B is selected from nucleotide bases.  34. The oligomer of claim 33, wherein the oligomer includes at least one LNA, while B is selected from adenine and guanine, and at least one LNA, while B is selected from thymine, cytosine, and uracil. 35. The oligomer according to any one of paragraphs. 29-34, while the substituent R ^{2 is} selected from hydrogen, hydroxyl and an optionally substituted C _1-6 alkoxy group, and R ^{1 *} , R ³ , R ⁵ and R ^{5 *} are hydrogen. 36. The oligomer according to any one of paragraphs. 1-35, while the internucleoside “bridge” of the LNA is selected from “bridges” 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``) <sub>2</sub> -, -SO-, -S (O) <sub>2</sub> -, -P (O) <sub>2</sub> -, -P (O, S) -, -P (S) <sub>2</sub> -, -PO (R``) -, -PO (OCH ₃ ) -, and -PO (NHR ^H ) -, where R ^{H is} selected from hydrogen and C _{1 -4-} alkyl, and R ^{11 is} selected from C _1-6 alkyl and phenyl. 37. The oligomer according to claim 36, wherein any internucleoside “bridge” of the LNA is selected from —CH ₂ —CH ₂ —CH ₂ -, —CH ₂ —CO — CH ₂ -, —CH ₂ —CHOH — 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 = NO-, -CH ₂ -NR ^H -O-, -CH ₂ -ON =, -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 ^H -, -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-, -OS (O) ₂ -O-, - OS (O) ₂ -CH ₂ -, -OS (O) ₂ -NR ^H -, -NR ^H -S (O) ₂ -CH ₂ -, -OS (O) ₂ -CH ₂ -, -OP (O ) ₂ -O-, -OP (O, S) -O-, -OP (S) ₂ -O-, -SP (O) ₂ -O-, -SP (O, S) -O-, -SP (S) ₂ -O-, -OP (O) ₂ -S-, -OP (O, S) -S-, -OP (S) ₂ -S-, -SP (O) ₂ -S-, - SP (O, S) -S-, -SP (S) ₂ -S-, -O-PO (R``) - O-, -O-PO (OCH <sub>3</sub> ) -O-, -O-PO ( BH <sub>3</sub> ) -O-, -O-PO (NHR <sup>N</sup> ) -O-, -OP (O) <sub>2</sub> -NR <sup>H</sup> -, -NR <sup>H</sup> -P (O) <sub>2</sub> -O-, -OP (O, NR <sup>H</sup> ) -O- and -O-Si (R``) ₂ -O-. 38. The oligomer of claim 37, wherein any internucleoside “bridge” of the LNA is selected from —CH ₂ —CO — NR ^H -, —CH ₂ —NR ^H —O—, —S-CH ₂ —O—, - O-P (O) ₂ -O-, -OP (O, S) -O-, -OP (S) ₂ -O-, -NRH-P (O) ₂ -O-, -OP (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 ″ are selected from C _1-6 alkyl and phenyl. 39. The oligomer according to any one of paragraphs. 1-38, despite the fact that each of the substituents R ^{1 *} , R ² , R ^{2 *} , R ³ , R ^{3 *} , R ^{4 *} , R ⁵ , R ^{5 *} , R ⁶ and R ^{6 *} , R ⁷ and R ^{7 *} in the composition of LNAs that are present and not involved in P, P ^* or diradical (diradicals) are independently selected from hydrogen, optionally substituted C _1-6 alkyl, optionally substituted C _2-6 alkenyl, hydroxyl, C _{1 -6} alkoxy groups, C _2-6 alkenyloxy groups, carboxyl, C _1-6 alkoxycarbonyl, C _1-6 alkylcarbonyl, formyl, amino groups, mono and di (C _1-6 alkyl) amino groups, carbamoyl, mono and di (C _1-6 alkyl) aminocarbonyl, C _1-6 alkylcarbonylamino groups, urea groups, azide groups, C _1-6 alkanoyloxy groups, sulfonic groups, sulfanyl, C _1-6 alkylthio groups, DNA intercalating groups, photochemically active groups, thermochemically active groups, chelating groups, reporter groups and ligands, and halogen, where there are two geminal substituents together can denote an oxo group and where R ^{N *} , in the case of presence and non-participation in the formation of a biradical, is selected from hydrogen and C _1-4 alkyl. 40. The oligomer according to any one of paragraphs. 1-39, while X is selected from —O—, —S— and —NR ^N -, and each of the substituents R ^{1 *} , R ² , R ^{2 *} , R ³ , R ^{3 *} , R ^{4 *} , R ⁵ , R ^{5 *} , R ⁶ , R ^{6 *} , R ⁷ and R ^{7 *} in the LNA, which are present and are not involved in P, P ^* or biradical (biradicals), represent hydrogen. 41. The oligomer according to any one of paragraphs. 1-40, while P represents a 5'-terminal group selected from hydrogen, hydroxyl, optionally substituted C _1-6 -alkyl, optionally substituted C _1-6 -alkoxy, optionally substituted C _1-6 -alkylcarbonyloxy, optionally a substituted aryloxy group, monophosphate, diphosphate, triphosphate and a group —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 intercalating groups, photochemically active groups, thermochemically active groups, chelating groups, reporter groups and ligands. 42. The oligomer according to any one of paragraphs. 1-41, while P ^* represents a 3'-terminal group selected from hydrogen, hydroxyl, an optionally substituted C _1-6 alkoxy group, an optionally substituted C _1-6 alkylcarbonyloxy group, an optionally substituted aryloxy group and a-W-A group ', 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 intercalating groups, photochemically active groups , thermochemically active groups, chelating groups, reporter groups and ligands. 43. The oligomer according to any one of paragraphs. 1-42, characterized by the formula V:
G- [NU-L] _{n (0)} - {[LNA-L] _{m (q)} - [Nu-L] _{n (q)} } _q -G ^* V
where q is 1-50;
each of n (0),. . . , n (q) is independently 0-10000;
each of m (1),. . . , m (q) is independently from each other 1-10000;
provided that the sum 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 native nucleosides and nucleoside analogues;
each LNA is independently a nucleoside analogue;
each L independently represents an internucleoside “bridge” between two groups selected from Nu and LNA, or L together with G ^* forms a 3'-terminal group; and
each LNA-L independently denotes a nucleoside analog of the general formula I

despite the fact that the substituents B, P, P ^* , R ^{1 *} , R ² , R ^{2 *} , R ³ , R ^{4 *} , R ⁵ and R ^{5 *} and X are defined in paragraphs. 1-42. 44. The oligomer according to any one of paragraphs. 1-42, further comprising a PNA-mono- or -oligomeric segment of the formula

while substituent B is defined above with respect to formula I, AASC is hydrogen or an amino acid side chain, t is 1-5 and w is 1-50.  45. The oligomer according to any one of paragraphs. 1-44, which is characterized by increased specificity for complementary single-stranded RNA and single-stranded DNA compared with natural oligonucleotide.  46. The oligomer according to any one of paragraphs. 1-44, which is characterized by increased affinity for complementary single-stranded RNA and single-stranded DNA compared with natural oligonucleotide.  47. The oligomer according to any one of paragraphs. 1-44, which is able to bind to the target sequence, which is part of a double-stranded DNA or double-stranded RNA molecule by the mechanism of "chain replacement" or due to the formation of triplex.  48. The oligomer according to any one of paragraphs. 1-44, which is more resistant to the action of nucleases in comparison with the native oligonucleotide.  49. The oligomer according to any one of paragraphs. 1-44, which exhibits catalytic activity against nucleic acids (LNA-modified ribozyme). 50. An oligomer comprising at least one nucleoside analog that affects a T _m oligomer with a complementary DNA oligonucleotide that is at least 2.5 ^° C higher than the corresponding unmodified control oligonucleotide that does not include any nucleoside analogues. 51. The oligomer of claim 50, wherein T _m is at least 2.5xN ^o C higher, where N is the number of nucleoside analogues. 52. An oligomer comprising at least one nucleoside analog that affects a T _m oligomer with a complementary RNA oligonucleotide that is at least 4.0 ^° C higher than the corresponding unmodified control oligonucleotide that does not include any nucleoside analogs . 53. The oligomer of claim 52, wherein T _m is at least 4.0xN ^° C higher, where N is the number of nucleoside analogues.  54. The oligomer according to claim 50 or 52, while such an oligomer is defined in any one of paragraphs. 1-49, in which at least one nucleoside analogue is characterized by the formula I, in which Deputy B is represented by a nucleotide base. 55. The oligomer according to claim 50, wherein said oligomer will be hybridized with a partially complementary DNA oligonucleotide, characterized by one or more mismatches, with said oligomer exhibits a decrease in T _m due to said mismatches, which is equal to or greater than that decrease that can be detected for the corresponding unmodified control oligonucleotide that does not include any nucleoside analogues. 56. The oligomer of claim 52, wherein said oligomer will hybridize with a partially complementary RNA oligonucleotide having one or more mismatches with said oligomer exhibits a decrease in T _m due to said mismatches that is equal to or greater than that decrease that can be detected for the corresponding unmodified control oligonucleotide that does not include any nucleoside analogues. 57. The oligomer according to claim 50 or 52, which is characterized by essentially the same sensitivity of the value of T _m to the ionic strength of the hybridization buffer as the corresponding unmodified control oligonucleotide.  58. The oligomer according to claim 50 or 52, which is modified by at least 30%.  59. The oligomer according to claim 50 or 52, which is characterized by significantly higher 3'-exonucleolytic stability compared to the corresponding unmodified control oligonucleotide.  60. The oligomer according to any one of paragraphs. 1-59 for sequence-specific target nucleic acid cleavage.  61. The oligomer according to any one of paragraphs. 1-59 for use in therapy, for example, in antisense, antigenic or gene-activating therapeutic methods.  62. The oligomer of claim 61, wherein the LNA-modified oligonucleotide recruits RNase-H.  63. The oligomer according to any one of paragraphs. 1-59 for use as an aptamer for therapeutic purposes.  64. The oligomer of claim 63, wherein the LNA-modified oligonucleotide includes at least one internucleoside “bridge” that is not a phosphodiester linkage.  65. The oligomer according to any one of paragraphs. 1-59, for diagnostic purposes, for example, for isolation, purification, amplification, detection, identification, quantification or selection of natural or synthetic nucleic acids.  66. The oligomer according to claim 65, wherein the oligonucleotide comprises a photochemically active group, a thermochemically active group, a chelating group, a reporter group, or a ligand that directly or indirectly detect this oligonucleotide or immobilize the oligonucleotide on a solid support.  67. The oligomer of claim 66, wherein the photochemically active group, thermochemically active group, chelating group, reporter group, or ligand comprise a spacer (K), wherein said spacer includes a chemically cleavable group. 68. The oligomer of claim 66, wherein the photochemically active group, the thermochemically active group, the chelating group, the reporter group, or the ligand are attached via a biradical (ie, are R ^* ) in at least one of the LNAs in oligonucleotide.  69. The oligomer according to claim 65 for the purpose of selecting and detecting natural or synthetic double-stranded or single-stranded nucleic acids, such as RNA or DNA.  70. The oligomer of Claim 65 for purifying natural double-stranded or single-stranded nucleic acids, such as RNA or DNA.  71. The oligomer according to claim 65 for use as a probe for in situ hybridization, for southern blotting, for dot-blot hybridization, reverse dot-blot hybridization, or for Northern blotting.  72. The oligomer according to claim 65 for the construction of an affinity pair.  73. The oligomer of claim 65 for use as a seed in a nucleic acid sequencing or chain growth reaction.  74. The oligomer of claim 65 for use as a seed in a nucleic acid amplification reaction.  75. The oligomer according to claim 74, while the seed is adapted in this way, the amplification reaction essentially proceeds according to a linear type.  76. The oligomer according to claim 74, while the seed is adapted in this way, the amplification reaction essentially proceeds according to an exponential type.  77. The oligomer according to any one of paragraphs. 74-76, while double-stranded DNA comprising at least one single-stranded end is formed in a nucleic acid amplification reaction.  78. The oligomer according to any one of paragraphs. 1-59 for use as an aptamer in molecular diagnostics.  79. The oligomer according to any one of paragraphs. 1-59 for use as an aptamer in catalytic processes mediated by RNA molecules.  80. The oligomer according to any one of paragraphs. 1-59 for use as an aptamer in the specific binding of antibiotics, drugs, amino acids, peptides, structural proteins, peptide receptors, peptide enzymes, saccharides, polysaccharides, biological cofactors, nucleic acids or triphosphates.  81. The oligomer according to any one of paragraphs. 1-59 for use as an aptamer in the separation of enantiomers in racemic mixtures due to stereospecific binding.  82. The oligomer according to any one of paragraphs. 1-59 for labeling cells.  83. The oligomer according to claim 82, even though such labeling will ensure the selection of labeled cells from unlabeled cells.  84. The oligomer according to any one of paragraphs. 1-59 for hybridization with non-coding cellular RNAs, such as tRNA, rRNA, snRNA and mcRNA, in vivo or in vitro.  85. The oligomer according to any one of paragraphs. 1-59 for use in the construction of an oligonucleotide comprising a fluorophore and a quencher arranged so that an oligonucleotide in a hybridized state can be distinguished from an oligonucleotide in an unbound state by amplifying the fluorescent signal of this probe.  86. The oligomer according to any one of paragraphs. 1-59 for use in the construction of probes such as Taq-man or Molecular Beacons. 87. Nucleoside analogue (hereinafter "LNA") of the General formula II

where Deputy B is selected from nucleotide bases, DNA intercalating agents, 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 *} ) -; one of the substituents R ² , R ^{2 *} , R ³ and R ^{3 *} is a group Q ^* ; each of Q and Q ^{* is} independently selected from hydrogen, azido group, halogen, cyano group, nitro group, hydroxyl, Prot-O-, Act-O-, mercapto group, Prot-S-, Act-S-, C _1-6 alkylthio group, amino groups, Prot-N (R ^H ) -, Act-N (R ^H ) -, mono- or di (C _1-6 alkyl) amino groups, optionally substituted C _1-6 alkoxy groups, optionally substituted C _1-6 - alkyl, optionally substituted C _2-6 -alkenyl, optionally substituted C _2-6 -alkeniloksigruppy optionally substituted C _2-6 -alkynyl, optionally substituted C _2-6 -alkiniloksigruppy, monophosphate, diphosphate, triphosphate, DNA-intercalation uyuschih groups, photochemically active groups, thermochemically active groups, chelating groups, reporter groups, ligands, carboxy, sulfonic groups, hydroxymethyl, Prot-O-CH ₂ -, of 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, and “Act” is the activation group for —OH, —SH and —NH (R ^H ), respectively, a 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 + 1} -, - (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 ^* ) -;
R ² and R ³ together denote a biradical selected from —O—, - (CR ^* R ^* ) _{r + s} -, - (CR ^* R ^* ) _r —O- (CR ^* R ^* ) _s -, - (CR ^* R ^* ) _r -S- (CR ^* R ^* ) _s - and - (CR ^* R ^* ) _r -N (R ^* ) - (CR ^* R ^* ) _s -; R ^{2 *} and R ³ together denote a biradical selected from -O- (CR ^* R ^* ) _{r + s} -, - (CR ^* R ^* ) _r -O- (CR ^* R ^* ) _s -, - (CR ^* R ^* ) _r -S- (CR ^* R ^* ) _s - and - (CR ^* R ^* ) _r -N (R ^* ) - (CR ^* R ^* ) _s -; R ³ and R ^{4 *} together denote a biradical selected from - (CR ^* R ^* ) _r -O- (CR ^* R ^* ) _s -, - (CR ^* R ^* ) _r -S- (CR ^* R ^* ) _s - and - (CR ^* R ^* ) _r - N (R ^* ) - (CR ^* R ^* ) _s -;
R ³ and R ⁵ together denote a biradical selected from - (CR ^* R ^* ) _r -O- (CR ^* R ^* ) _s -, - (CR ^* R ^* ) _r -S- (CR ^* R ^* ) _s - and - (CR ^* R ^* ) _r - N (R ^* ) - (CR ^* R ^* ) _s -;
or
R ^{1 *} and R ^{4 *} together denote a biradical selected from - (CR ^* R ^* ) _r -O- (CR ^* R ^* ) _s -, - (CR ^* R ^* ) _r -S- (CR ^* R ^* ) _s - and - (CR ^* R ^* ) _r -N (R ^* ) - (CR ^* R ^* ) _s -; R ^{1 *} and R ^{2 *} together denote a biradical selected from - (CR ^* R ^* ) _r -O- (CR ^* R ^* ) _s -,
- (CR ^* R ^* ) _r -S- (CR ^* R ^* ) _s - and - (CR ^* R ^* ) _r -N (R ^* ) - (CR ^* R ^* ) _s -;
while each R is independently selected from hydrogen, halogen, azido group, cyano group, nitro group, hydroxyl, mercapto group, amino group, mono- or di (C _1-6 alkyl) amino group, optionally substituted with C _1-6 alkoxy group optionally substituted C _1-6 alkyl, DNA intercalating groups, photochemically active groups, thermochemically active groups, chelating groups, reporter groups and ligands, and (or) two adjacent (non-heminal) R ^* can together represent a double bond, and each of r and s are 0-3, provided that the sum r + s is 1-4;
each of the substituents R ^{1 *} , R ² , R ^{2 *} , R ³ , R ^{4 *} , R ⁵ and R ^{5 *} , which are not involved in Q, Q ^* or a diradical, is independently selected from hydrogen, optionally substituted with C _1-12 -alkyl, optionally substituted C _2-12 alkenyl, optionally substituted C _2-12 alkynyl, hydroxyl, 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 -amine ) 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 groups, carbamido, C _1-6 alkanoyloxy groups, sulfonic groups, C _1-6 alkylsulfonyloxy groups, nitro groups, azido groups, sulfanyl, C _1-6 alkylthio groups, halogen, DNA intercalating groups, photochemically active groups , thermochemically active groups, chelating groups, reporter groups and ligands, where aryl and heteroaryl may be optionally substituted and where two g the radical substituents together can define an oxo group, a thioxo group, an imino group or an optionally substituted methylene or together they can form a spiro bio radical including a 1-5-carbon alkylene chain, which is optionally interrupted and (or) terminated by one or more heteroatoms / groups selected from -O-, -S- and - (NR ^N ) -, where R ^{N is} selected from hydrogen and C _1-4 -alkyl and where two adjacent (non-heminal) substituents may represent an additional double bond; and R ^N , when present and not included in the diradical, is selected from hydrogen and C _1-4 alkyl;
and their basic salts and acid addition salts;
under the first condition that
R ² and R ³ together do not denote a diradical selected from —O — CH ₂ —CH ₂ - and —O — CH ₂ —CH ₂ —CH ₂ -,
R ³ and R ⁵ together do not denote a diradical selected from —CH ₂ —CH ₂ -, —O — CH ₂ - and —O — Si ( ⁱ Pr) ₂ —O — Si ( ⁱ Pr) ₂ —O—;
and under the second condition that any chemical group (including any nucleotide base) that is reactive under conditions that occur during the synthesis of oligonucleotides is not necessarily protected in its functional component.  88. The nucleoside analogue of claim 87, wherein group B is selected from nucleotide bases and nucleotide bases protected by their functional components. 89. The nucleoside analogue according to any one of paragraphs. 87-88, with X being selected from —O—, —S— and —N (R ^{N *} ) -. 90. The nucleoside analogue according to any one of paragraphs. 87-89, despite the fact that each of the substituents R ^{1 *} , R ² , R ^{2 *} , R ³ , R ^{3 *} , R ^{4 *} , R ⁵ and R ^{5 *} when they are present and are involved in the formation of Q, Q ^* or a biradical independently selected from hydrogen, optionally substituted C _1-6 alkyl, optionally substituted C _2-6 alkenyl, hydroxyl, C _1-6 alkoxy, C _2-6 alkenyloxy, carboxyl, C _{1 -6-} alkoxycarbonyl, C _2-6 -alkylcarbonyl, formyl, amino, mono- and di (C _1-6 -alkyl) amino, carbamoyl, mono- and di (C _1-6 -alkyl) aminocarbonyl, C _1-6 -alkylcarbonylamino groups, carbamido, azido groups, C _1-6 alkanoys oxy groups, sulfonic groups, sulfanyl, C _1-6 alkylthio groups, DNA intercalating groups, photochemically active groups, thermochemically active groups, chelating groups, reporter groups, ligands and halogen, where two geminal substituents together can represent an oxo group, and where R ^{N N *} if present and not involved in the formation of a biradical, they are selected from hydrogen and C _1-4 alkyl, provided that any hydroxyl, amino group, mono (C _1-6 alkyl) amino group, sulfanyl and carboxyl are optionally protected. 91. The nucleoside analogue according to any one of paragraphs. 87-90, in which each of the substituents R ^{1 *} , R ² , R ^{2 *} , R ³ , R ^{3 *} , R ^{4 *} and R ⁵ , R ^{5 *} , R ⁶ , R ^{6 *} , if present and not involved in the formation of Q ^* or biradical, denotes hydrogen. 92. The nucleoside analogue according to any one of paragraphs. 87-91, while R ^{3 *} forms P ^* . 93. The nucleoside analogue according to any one of paragraphs. 87-92, while Q is independently selected from hydrogen, azido group, halogen, cyano group, nitro group, hydroxyl, Prot-O-, mercapto group, Prot-S-, C _1-6 alkylthio group, amino group, Prot-N (R ^H ) -, a mono- or di (C _1-6 alkyl) amino group, an optionally substituted C _1-6 alkoxy group, an optionally substituted C _1-6 alkyl, an optionally substituted C _2-6 alkenyl, an optionally substituted C _{2- 6} -alkeniloksigruppy optionally substituted C _2-6 -alkynyl, optionally substituted C _2-6 -alkiniloksigruppy, monophosphate, diphosphate, triphosphate, DNA-intercalating groups, otohimicheski active groups, thermochemically active groups, chelating groups, reporter groups, ligands, carboxy, sulfonic
groups, hydroxymethyl, Prot-O-CH ₂ -, aminomethyl, Prot-N (R ^H ) -CH ₂ -, carboxymethyl, sulfonomethyl, where "Prot" denotes a protecting group for —OH, —SH and —NH (R ^H ) respectively, a R ^{H is} selected from hydrogen and C _1-6 alkyl; and
Q ^{* is} selected from hydrogen, azido group, halogen, cyano group, nitro group, hydroxyl, Act-O-, mercapto group, Act-S-, C _1-6 alkylthio group, amino group, Act-N (R ^H ) -, mono or di (C _1-6 alkyl) amino group, optionally substituted C _1-6 alkoxy group, optionally substituted C _1-6 alkyl, optionally substituted C _2-6 alkenyl, optionally substituted C _2-6 alkenyloxy group, optionally substituted C _{2 -6} -alkynyl, optionally substituted C _2-6 -alkiniloksigruppy, DNA-intercalating groups, photochemically active groups, thermochemically active groups, x latiruyuschih groups, reporter groups, ligands, carboxy, sulfonic group, where Act is an activation group for -OH, -SH and -NH (R ^H), respectively, and R ^H is selected from H and C _1-6 alkyl. 94. The nucleoid analogue according to any one of paragraphs. 87-93 of the general formula IIa

where the substituents Q, B, R ^{1 *} , R ² , R ^{2 *} , R ³ , R ^{3 *} , R ^{4 *} , R ⁵ and R ^{5 * are} defined in paragraphs. 87-93. 95. The nucleoside analogue of claim 94, wherein R ^{3 *} forms P ^* . 96. The nucleoside analogue of claim 95, wherein R ^{2 *} and R ^{4 *} together form a diradical. 97. The nucleoside analogue of claim 96, wherein X is O, R ^{2 is} selected from hydrogen, hydroxyl, and an optionally substituted C _1-6 alkoxy group, and R ^{1 *} , R ³ , R ^5, and R ^{5 *} are hydrogen . 98. The nucleoside analogue of claim 97, 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 -. 99. The nucleoside analogue of claim 98, wherein the biradical is selected from —O — CH ₂ -, —S — CH ₂ -, and —N (R ^N ) —CH ₂ -.  100. The nucleoside analogue according to any one of paragraphs. 96-99, while B is selected from nucleotide bases.  101. The nucleoside analogue of claim 100, wherein the oligomer includes at least one LNA in which B is selected from adenine and guanine, and at least one LNA in which B is selected from thymine, cytosine, and uracil. 102. The nucleoside analogue of claim 97, wherein the biradical is - (CH ₂ ) _2-4 -, preferably - (CH ₂ ) ₂ -. 103. The nucleoside analogue of claim 95, wherein R ² and R ³ together form a diradical. 104. The nucleoside analogue of claim 103, wherein X is O, R ^{2 is} selected from hydrogen, hydroxyl and an optionally substituted C _1-6 alkoxy group, and R ^{1 *} , R ^{4 *} , R ⁵ and R ^{5 *} are hydrogen. 105. The nucleoside analogue of claim 104, wherein the biradical is the group - (CH ₂ ) _0-1 —O— (CH ₂ ) _1-3 -. 106. The nucleoside analogue of claim 104, wherein the biradical is the group - (CH ₂ ) _1-4 -. 107. The nucleoside analogue according to any one of paragraphs. 95-106, while one of R ^{* is} selected from hydrogen, hydroxyl, optionally substituted C _1-6 alkoxy groups, optionally substituted C _1-6 alkyl, DNA intercalating groups, photochemically active groups, thermochemical active groups, chelating groups, reporter groups and ligands, and any of the other R ^* substituents are hydrogen. 108. The nucleoside analogue according to any one of paragraphs. 95-107, despite the fact that the R ^* group in the biradical of at least one LNA is selected from DNA intercalating groups, photochemically active groups, thermochemical active groups, chelating groups, reporter groups and ligands.  109. The nucleoside analogue according to any one of paragraphs. 95-108, while the LNA corresponds to the general formula Ia. 110. The nucleoside analogue of claim 87 of general formula IIa

where X is represented by —O—; B is selected from nucleotide bases, DNA intercalating groups, photochemically active groups, thermochemically active groups, chelating groups, reporter groups and ligands; R is represented by the group Q ^* ; each of Q and Q ^{* is} independently selected from hydrogen, an azido group, a halogen, a cyano group; nitro groups, hydroxyl, Prot-O-, Act-O-, mercapto groups, Prot-S-, Act-S-, C _1-6 alkylthio groups, amino groups, Prot-N (R ^H ) -, Act-N (R ^H ) -, mono- or di (C _1-6 -alkyl) amino group, optionally substituted C _1-6 alkoxy group, optionally substituted C _1-6 alkyl, optionally substituted C _2-6 alkenyl, optionally substituted C _2-6 -alkenyloxy group, optionally substituted C _2-6 alkynyl, optionally substituted C _2-6 alkynyloxy group, monophosphate, diphosphate, triphosphate, DNA intercalating groups, photochemically active groups, thermochemically active groups, I chelate groups, reporter groups, ligands, carboxyl, sulfonic group, 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, and Act is an activation group for —OH, —SH and —NH (R ^H ) respectively, a R ^{H is} selected from hydrogen and C _1-6 alkyl;
R ^{2 *} and R ^{4 *} together denote a biradical selected from -O-, -S-, -N (R ^* ) -, - (CR ^* R ^* ) _{r + s + 1} -, - (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 ^* ) -; wherein each R ^{* is} independently selected from hydrogen, halogen, azido group, cyano group, nitro group, hydroxyl, mercapto group, amino group, mono- or di (C _1-6 alkyl) amino group, optionally substituted C _1-6 alkoxy group, optionally substituted C _1-6 alkyl, DNA intercalating groups, photochemically active groups, thermochemically active groups, chelating groups, reporter groups and ligands, and (or) two adjacent (non-heminal) R ^* can together denote a double bond, and each of r and s is 0-3 provided that the sum r + s is 1-4; each of the substituents R ^{1 *} , R ² , R ³ , R ⁵ and R ^{5 * is} independently selected from hydrogen, optionally substituted C _1-6 alkyl, optionally substituted C _2-6 alkenyl, hydroxyl, C _1-6 alkoxy , C _2-6 alkenyloxy groups, carboxyl, C _1-6 alkoxycarbonyl, C _1-6 alkylcarbonyl, formyl, amino groups, mono and di (C _1-6 alkyl) amino groups, carbamoyl, mono and di (C _1-6 alkyl) aminocarbonyl, C _1-6 -alkilkarbonilaminogruppy, carbamido, azido, C _1-6 -alkanoiloksigruppy, a sulfonic group, sulfanyl, C _1-6 alkylthio, DNA-intercalating groups photochemically acti explicit groups, thermochemically active groups, chelating groups, reporter groups and ligands, and halogen, where two geminal substituents together can represent an oxo group; and their basic salts and acid addition salts; and provided that any chemical group (including any nucleotide base) that is reactive under the conditions created during the synthesis of the oligonucleotide may optionally be protected in its functional component. 111. The nucleoside analogue of claim 110, wherein one of R ^{* is} selected from hydrogen, hydroxyl, optionally substituted C _1-6 alkoxy, optionally substituted C _1-6 alkyl, DNA intercalating groups, photochemically active groups, thermochemically active groups, chelating groups, reporter groups and ligands, and any of the other R ^* substituents are hydrogen. 112. The nucleoside analogue according to any one of paragraphs. 110-111, while the diradical is selected from —O—, - (CH ₂ ) _0-1 —O- (CH ₂ ) _1-3 -, - (CH ₂ ) _0-1 —S- (CH ₂ ) _1-3 -, - (CH ₂ ) _0-1 -N (R ^N ) - (CH ₂ ) _1-3 - and - (CH ₂ ) _2-4 -. 113. The nucleoside analogue of claim 112, wherein the biradical is selected from —O — CH ₂ -, —S — CH ₂ -, and —N (R ^N ) —CH ₂ -.  114. The nucleoside analogue according to any one of paragraphs. 110-113, while B is selected from nucleotide bases.  115. The nucleoside analogue of claim 114, wherein the oligomer includes at least one LNA in which B is selected from adenine and guanine, and at least one LNA in which B is selected from thymine, cytosine and uracil . 116. The nucleoside analogue of claim 110, wherein B is a nucleotide base, X is —O—, R ^{2 *} and R ^{4 * are} together a biradical selected from - (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 - where R ^{* is} selected from hydrogen and C _1-4 alkyl, Q is Prot-O-, R ^{3 *} is Q ^* , which forms Act-OH, and each of R ^{1 *} , R ² , R ³ , R ⁵ and R ^{5 *} represents hydrogen, where “Act” and “prot” are defined in 58. 117. The nucleoside analogue of claim 110, wherein B is a nucleotide base, X is —O—, R ^{2 *,} and R ^{4 *} together are a diradical selected from - (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 - where R ^{* is} selected from hydrogen and C _1-4 alkyl, Q is selected from hydroxyl, mercapto group, C _1-6 alkylthio group, amino group, mono or di (C _1-6 alkyl) amino group, optionally substituted with C _{1- 6} alkoxy, optionally substituted C _2-6 -alkeniloksigruppy optionally substituted C _2-6 -alkiniloksigruppy, monophosphate, diphosphate, and triphosphate, R ^{3 *} pre Substituting group Q ^*, which is selected from hydrogen, azido, halogen, cyano, nitro, hydroxyl, mercapto, C _1-6 alkylthio, amino, 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 and optionally substituted C _2-6 -alkynyloxy, R ^{3 is} selected from H, optionally substituted C _1-6 alkyl, optionally substituted C _2-6 alkenyl and optionally substituted C _2-6 alkynyl, and each of the substituents R ^{1 *} , R ² , R ⁵ and R ^{5 *} is hydrogen. 118. The nucleoside analogue of claim 110, wherein B is represented by a nucleotide base, X is represented by —O—, R ² and R ³ together denote a diradical selected from - (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 -, where R ^{N is} selected from H and C _1-4 alkyl, Q is selected from hydrogen, mercapto group, C _1-6 alkylthio group, amino group, mono or di (C _1-6 alkyl) amino group, optionally substituted with C _1-6 - alkoxy, optionally substituted C _2-6 -alkeniloksigruppy optionally substituted C _2-6 -alkiniloksigruppy, monophosphate, diphosphate, and triphosphate, R ^{3 *} representations Q ^* group selected from hydrogen, azido group, halogen, cyano group, nitro group, hydroxyl, mercapto group, C _1-6 alkylthio group, amino group, mono or di (C _1-6 alkyl) amino group of optionally substituted C _1-6 an alkoxy group, an optionally substituted C _1-6 alkyl, an optionally substituted C _2-6 alkenyl, an optionally substituted C _2-6 alkynyloxy group, an optionally substituted C _2-6 alkynyl, an optionally substituted C _2-6 alkynyloxy, and each of the substituents R ^{1 *} , R ^{2 *} , R ^{4 *} , R ⁵ and R ^{5 *} are hydrogen.  119. The nucleoside analogue according to claim 87, which is selected from (1R, 3R, 4R, 7S) -7- (2-cyanoethoxy (diisopropylamino) phosphinoxy-1- (4,4'-dimethoxytrityloxymethyl) -3- (thymine-1 -yl) -2,5-dioxa-bicyclo [2.2.1] heptane, (1R, 3R, 4R, 7S) -7-hydroxy-1- (4,4'-dimethoxytrityloxymethyl) -3- (thymine-1- il) -2,5-dioxabicyclo- [2.2.1] heptane-7-O- (2-chlorophenylphosphate) and (1R, 3R, 4R, 7S) -7-hydroxy-1- (4,4'-dimethoxytrityloxymethyl) -3- (thymin-1-yl) -2,5-dioxabicyclo- [2.2.1] heptan-7-O- (N-phosphonate) and the corresponding -3- (cytosin-1-yl) n, -3- (uracil-1-yl) n, -3- (adenin-1-yl) n and -3- (guanine-3-yl) n analogues.  120. The nucleoside analogue according to any one of paragraphs. 87-119 to obtain the LNA-modified oligonucleotide (oligomer) corresponding to any one of paragraphs. 1-59.  121. The nucleoside analogue of claim 120, wherein the LNA-modified oligonucleotide includes conventional nucleosides, such as ribonucleosides and / or deoxyribonucleotides, as well as modified nucleosides that are different from those defined in paragraph 87.  122. The nucleoside analogue of claim 120, wherein the addition of LNA modulates the ability of such an oligonucleotide to serve as a substrate for enzymes active against nucleic acids.  123. The nucleoside analogue according to any one of paragraphs. 87-119 to obtain a complex of LNA-modified oligonucleotide and a compound selected from proteins, amplicons, enzymes, polysaccharides, antibodies, haptens, peptides and PNA.  124. The nucleoside analogue according to any one of paragraphs. 87-119 as a substrate for enzymes active against nucleic acids.  125. The nucleoside analogue of Claim 124, wherein the substituent Q in Formula I in Clause 87 is triphosphate.  126. The nucleoside analogue of claim 124, wherein LNA is used as a substrate for DNA and RNA polymerases.  127. The nucleoside analogue according to any one of paragraphs. 87-119 as a medicine.  128. The nucleoside analogue according to any one of paragraphs. 87-119 for diagnostic purposes.  129. The nucleoside analogue according to any one of paragraphs. 87-119 for constructing a solid support to which LNA-modified oligonucleotides having different sequences are attached.  130. The nucleoside analogue of claim 129, wherein the LNA-modified oligonucleotides are attached at their specified location. 131. The nucleoside analogue of claim 129, wherein the LNAs are used to equalize the T _m values of the corresponding unmodified control oligonucleotides.  132. The nucleoside analogue of claim 129, wherein the LNA-modified oligonucleotides are characterized by increased affinity for complementary single-stranded DNA or single-stranded RNA compared to a natural oligonucleotide.  133. The nucleoside analogue of claim 129, wherein the LNA-modified oligonucleotides are characterized by increased specificity for complementary single-stranded DNA or single-stranded RNA compared to a natural oligonucleotide.  134. The conjugate of the LNA-modified oligonucleotide (oligomer), as defined in any one of paragraphs. 1-59, and compounds selected from proteins, amplicons, enzymes, polysaccharides, antibodies, haptens, peptides and PNA.  135. The material of a solid support with immobilized thereon is optionally protected at its base and optionally protected at 5'-OH LNA.  136. The complex formed by more than one LNA-modified oligonucleotide (oligomer), as defined in any one of paragraphs. 1-59, for example, in antisense, antigenic, or gene-activating therapeutic methods.  137. A kit for the isolation, purification, amplification, detection, identification, quantitative analysis or selection of native or synthetic nucleic acids, despite the fact that this kit includes a reaction device and one or more LNA-modified oligonucleotides (oligomers) as defined in any one of claims . 1-59.  138. The kit of claim 137, wherein the LNA-modified oligonucleotides are immobilized on said reaction device.  139. A kit for the isolation, purification, amplification, detection, identification, quantitative analysis or selection of natural or synthetic nucleic acids, despite the fact that this kit includes a reaction device and one or more LNAs as defined in any one of paragraphs. 87-119.  140. The kit of claim 139, wherein the LNAs are immobilized on said reaction device.