Oligonucleotides with inverted polarity

Claim 2

An oligonucleotide comprising a first nucleotide sequence containing at least three nucleotide residues, said sequence having either 3'→5' or 5'→3' polarity, and, coupled thereto, a second nucleotide sequence containing at least three nucleotide residues, said second sequence having polarity inverted from that of the first sequence.

Claim 3

The oligonucleotide of claim 1 wherein the 5' position of a nucleotide at the 5' end of the first sequence is covalently bonded to the 5' position of the nucleotide at the 5' end of the second sequence, or wherein the 3' position of a nucleotide at the 3' end of the first sequence is covalently bonded to the 3' position of the nucleotide at the 3' end of the second sequence.

Claim 4

The oligonucleotide of claim 1 wherein the base of the nucleotide at the 5' end of the first sequence is covalently bonded to the base of the nucleotide at the 5' end of the second sequence, or wherein the base of the nucleotide at the 3' end of the first sequence is covalently bonded to the base of the nucleotide at the 3' end of the second sequence.

Claim 5

The oligonucleotide of claim 1 wherein the base of the nucleotide at the 5' end of the first sequence is covalently bonded to the 5' position of the nucleotide at the 5' end of the second sequence, or wherein the 5' position of the nucleotide at the 5' end of the first sequence is covalently bonded to the base of the nucleotide at the 5' end of the second sequence, or wherein the base of the nucleotide at the 3' end of the first sequence is covalently bonded to the 3' position of the nucleotide at the 3' end of the second sequence, or wherein the 3' position of the nucleotide at the 3' end of the first sequence is covalently bonded to the base of the nucleotide at the 3' end of the second sequence.

Claim 6

The oligonucleotide of claim 1 wherein said first and second sequences are covalently bonded through a linkage comprising a linker residue wherein said linker residue is of a molecule comprising two functional groups involved in the linkage, each said functional group selected from the group consisting of an amine, a sulfhydryl, and a hydroxyl.

Claim 7

The oligonucleotide of claim 5 wherein said linker residue is a residue of a diol or diamine.

Claim 8

The oligonucleotide of claim 6 wherein said diol or diamine is of the formula: HZ(CH 2 ) n1 ZH, wherein each Z is independently O or NH, and wherein n1 is an integer of 1-15 and one or more of said CH 2 groups may be replaced by O, S, or NH, provided said replacement is not adjacent to a heteroatom.

Claim 9

The oligonucleotide of claim 7 wherein the diol or diamine is of the formula HZ(CH 2 CH 2 O) n2 H, wherein Z is O or NH and wherein n2 is an integer of 1-5.

Claim 10

The oligonucleotide of claim 6 wherein said diol or diamine is of the formula HZCH 2 (CX 2 CX 2 ) n3 CH 2 ZH, wherein each Z is independently O or NH, and wherein n3 is an integer of 1-7 and each pair of X or adjacent C independently are H or together are a π bond.

Claim 11

The diol or diamine of claim 6 wherein said diol or diamine is of the formula HZCH 2 (CX 2 CX 2 ) n4 CH 2 (CX 2 CX 2 ) n5 CH 2 ZH, wherein each Z is independently O or NH, and wherein n4 and n5 are integers of 0-7 and wherein the sum of n4 and n5 is not greater than 7 and wherein each pair of X or adjacent C independently are H or together are a π bond.

Claim 12

The oligonucleotide of claim 6 wherein said diol or diamine contains a ring system.

Claim 13

The oligonucleotide of claim 11 wherein said ring system is nonaromatic.

Claim 14

The oligonucleotide of claim 12 wherein said nonaromatic ring is piperidine, piperazine, furan, tetrahydrofuran, cyclohexene, cyclopentene, cyclopentane or cyclohexane.

Claim 15

The oligonucleotide of claim 13 wherein the diol is selected from the group consisting of cis- or trans-3-4-dihydroxyfuran, cis- or trans-2-hydroxymethyl-3-hydroxyfuran, and cis- or trans-2-hydroxymethyl-4-hydroxyfuran, said furan either further unsubstituted, or further substituted with one or two noninterfering alkyl(1-4C) substituents.

Claim 16

The oligonucleotide of claim 11 wherein said ring system is aromatic.

Claim 17

The oligonucleotide of claim 15 wherein said aromatic ring is benzene or naphthalene.

Claim 18

The oligonucleotide of claim 16 wherein said diol is selected from the group consisting of 1,2-dihydroxymethylbenzene; 1,4-dihydroxymethylbenzene; 1,3-dihydroxymethylbenzene; 2,6-dihydroxymethylnaphthalene; 1,5-dihydroxymethylnaphthalene; 1,4-bis(3-hydroxy propenyl)benzene; 1,3-bis(3-hydroxypropenyl)benzene; 1,2-bis (3-hydroxypropenyl)benzene; 2,6-bis(3-hydroxypropenyl)naphthalene; 1,5-bis (3-hydroxypropynyl)naphthalene, 1,4-bis(3-hydroxypropynyl)benzene; 1,3-bis(3-hydroxypropynyl)benzene; 1,2-bis(3-hydroxypropynyl)benzene; 2,6-bis(3-hydroxypropynyl) naphthalene; and 1,5-bis(3-hydroxypropynyl)naphthalene.

Claim 19

The oligonucleotide of claim 1 wherein said first and second sequence are covalently bonded through a linkage of the formula: ##STR16## wherein: Y is H, --OR, --SR, --NR 2 , O 31 , or S - ; X is O, S, or NR; wherein each R is independently H, alkyl (1-12C), aryl (6-12C), aralkyl (7-20C) or alkaryl (7-20C); n is 0 or 1; and A is the residue of a linker group wherein said residue of a linker group is of a molecule comprising two functional groups involved in the linkage, each said functional group selected from the group consisting of an amine, a sulfhydryl, and a hydroxyl.

Claim 20

The oligonucleotide of claim 18 wherein all X are O.

Claim 21

The oligonucleotide of claim 19 wherein all Y are O.

Claim 22

The oligonucleotide of claim 18 wherein said linker residue, A, is a residue of a diol or diamine.

Claim 23

The oligonucleotide of claim 21 wherein said linker residue comprises a ring system.

Claim 24

The oligonucleotide of claim 22 wherein said ring is aromatic.

Claim 25

The oligonucleotide of claim 23 wherein said aromatic ring is benzene or naphthalene.

Claim 26

The oligonucleotide of claim 24 wherein said diol is selected from the group consisting of 1,2-dihydroxymethylbenzene; 1,4-dihydroxymethylbenzene; 1,3-dihydroxymethylbenzene; 2,6-dihydroxymethylnaphthalene; 1,5-dihydroxymethylnaphthalene; 1,4-bis(3-hydroxy propenyl)benzene; 1,3-bis(3-hydroxypropenyl)benzene; 1,2-bis(3-hydroxypropenyl)benzene; 2,6-bis(3-hydroxypropenyl)naphthalene; 1,5-bis(3-hydroxypropenyl) naphthalene; 1,4-bis(3-hydroxypropynyl)benzene; 1,3-bis(3-hydroxypropynyl)benzene; 1,2-bis(3-hydroxypropynyl)benzene; 2,6-bis(3-hydroxypropynyl) naphthalene; and 1,5-bis(3-hydroxypropynyl)naphthalene.

Claim 27

The oligonucleotide of claim 22 wherein said ring is nonaromatic.

Claim 28

The oligonucleotide of claim 26 wherein said nonaromatic ring is piperidine, piperazine, furan, tetrahydrofuran, cyclohexene, cyclopentene, cyclopentane or cyclohexane.

Claim 29

The oligonucleotide of claim 27 wherein the diol is selected from the group consisting of cis- or trans-3-4-dihydroxyfuran, cis- or trans-2-hydroxymethyl-3-hydroxyfuran and cis- or trans-2-hydroxymethyl-4-hydroxyfuran, said furan either further unsubstituted, or further substituted with one or two noninterfering alkyl (1-4C) substituents.

Claim 30

The oligonucleotide of claim 21 wherein said diol or diamine is of the formula: HZ(CH 2 ) n1 ZH, wherein each Z is independently O or NH, and wherein n1 is an integer of 1-10 and one or more of said CH 2 groups may be replaced by O, S, or NH, provided said replacement is not adjacent to a heteroatom.

Claim 31

The oligonucleotide of claim 29 wherein the diol or diamine is of the formula HZ(CH 2 CH 2 O) n2 H, wherein Z is O or NH and wherein n2 is an integer of 1-5.

Claim 32

The oligonucleotide of claim 22 wherein said diol or diamine is of the formula HZCH 2 (CX 2 CX 2 ) n3 CH 2 ZH, wherein each Z is independently O or NH, and wherein n3 is an integer of 1-7 and each pair of X is an adjacent C independently H or a π bond.

Claim 33

The oligonucleotide of claim 21 wherein said diol or diamine is of the formula HZCH 2 (CX 2 CX 2 ) n4 CH 2 (CX 2 CX 2 ) n5 CH 2 ZH, wherein each Z is independently O or NH, and wherein n4 and n5 are integers of 0-7 and wherein the sum of n4 and n5 is not greater than 7 and wherein each pair of X is an adjacent C independently H or a participant in a π bond.