Lipohillic oligonucleotide analogs

1. A lipophilic oligonucleotide comprising a phosphate glycerol unit containing at least one aliphatic unsaturated carbon bond according to formula I

with

Oligonucleotide=an unmodified or modified nucleic acid of 2-1000 nucleotides in length

R=a bond or a linker unit

Y=OH, SH or NH substituted with one residue comprising hydrogen or branched or unbranched and/or substituted or unsubstituted alkyl, aryl and/or alkyl aryl residue with 10 to 30 carbon atoms

X and Z=independently O, S or N, substituted with one residue comprising hydrogen or branched or unbranched and/or substituted or unsubstituted alkyl, aryl and/or alkyl aryl residue with 10 to 30 carbon atoms

R1, R2=branched or unbranched and/or substituted or unsubstituted alkyl, aryl and/or alkylaryl residue with 10 to 30 carbon atoms, with the proviso that at least one of the residues R1 or R2 comprises at least one aliphatic carbon-carbon double bond.

2. Lipophilic oligonucleotide according to claim 1 as defined in Formula III

wherein R, X, Y, Z, R1, and R2 have the same meaning as in Formula I and ODN stands as abbreviation for oligonucleotide with the same meaning as in Formula I.

3. Lipophilic oligonucleotide according to claim 1 as defined in Formula IV

wherein R, X, Y, Z, R1, R2 have the same meaning as in Formula I and ODN stands as abbreviation for oligonucleotide with the same meaning as in Formula I.

4. A lipophilic oligonucleotide according to claim 1 wherein R is a bifunctional linker unit and is selected from the group

branched or unbranched and/or substituted or unsubstituted alkyl, aryl and/or alkyl aryl residue with 1 to 100 carbon atoms

sugar

amino-, thiol-, ethylene glycol-, in particular, triethyleneglycol and hexaethyleneglycol modified C3-, C-6 and C-12-linkers optionally having two functional groups, such as e.g. amino-, thiol-, carboxyl or hydroxyl functions which allow attachment of an oligonucleotide on one side and a lipophilic residue on the other side

reversible linker, which can be designed to undergo a chemical or enzymatic cleavage reaction.

5. Method for the preparation of oligonucleotides of claim 1 , wherein Oligonucleotide-R—OH is coupled with a phosphate glycerol unit containing one lipophilic residue according to formula II

With

R5, R6=Methyl, Ethyl, Propyl, isopropyl, Butyl residue, or R1 and R2 forming a cyclic aliphatic residue

R4=protecting group, selected from the group of alkyl, substituted alkyl, alkylaryl, and β-cyanoalkyl

R1 and R2=same meaning as in Formula I

and subsequently oxidized and deprotected to yield oligonucleotides of formula I.

6. Method according to claim 5 wherein a compound according to formula VI is used as phosphate glycerol unit containing one lipophilic residue

With

R5, R6=Methyl, Ethyl, Propyl, isopropyl, Butyl residue, or R1 and R2 forming a cyclic aliphatic residue

R4=protecting group, selected from the group of alkyl, substituted alkyl, alkylaryl, β-cyanoalkyl, β-phenylethyl.

7. The method according to claim 5 wherein a compound according to formula VII is used as phosphate glycerol unit containing one lipophilic residue

With

R5, R6=Methyl, Ethyl, Propyl, isopropyl, Butyl residue, or R1 and R2 forming a cyclic aliphatic residue

R4=protecting group, selected from the group of alkyl, substituted alkyl, alkylaryl, β-cyanoalkyl, β-phenylethyl.

8. The method according to claim 5 , wherein a compound according to formula VIII is used as phosphate glycerol unit containing one lipophilic residue

with DMTr=4,4′-Dimethoxytrityl residue.