RU2002105016A - CONJUGATES AND METHOD FOR PRODUCING THEM, AND ALSO THEIR APPLICATION FOR THE TRANSPORT OF MOLECULES THROUGH BIOLOGICAL MEMBRANES - Google Patents

Claims (26)

1. The conjugate consisting of a transported molecule and at least one aryl residue of the formula (I)

wherein aryl means a group which contains at least one aromatic type ring; X is O or N; Y is O, S or NH-R ² ; R ¹ means a substituted or unsubstituted (C ₁ -C ₂₃ ) -alkyl radical, which may be linear or branched and may contain double and / or triple bonds; R ² means a substituted or unsubstituted (C ₁ -C ₁₈ ) -alkyl radical, which may be linear or branched and may contain double and / or triple bonds; n ≥ 1, moreover, the aryl residue is bound to the transported molecule either directly via a chemical bond or indirectly through a chemical group, the chemical group being not a CH ₂ -S group when the transported molecule is bound via an internucleotide phosphodiester bond. 2. The conjugate according to claim 1, characterized in that the transported molecule is a macromolecule with a molecular weight> 500 Da. 3. The conjugate according to one or more of claims 1 and 2, characterized in that the transported molecule is a polynucleotide, polypeptide or polysaccharide. 4. The conjugate according to one or more of claims 1 to 3, characterized in that the transported molecule is an oligonucleotide. 5. The conjugate according to claim 4, characterized in that the oligonucleotide is modified. 6. The conjugate according to claim 1, characterized in that the transported molecule is a low molecular weight compound with a molecular weight of <500 Da. 7. The conjugate according to claim 6, characterized in that the low molecular weight compound is a mononucleotide. 8. The conjugate according to one or more of claims 1 to 7, characterized in that the chemical group together with the aryl residue corresponds to the formula (II)

wherein aryl, X, Y, and R ¹ are as defined above; R ³ means a chemical group, wherein R ³ preferably means a —C group (= 0) or —NH — C group (= S). 9. The conjugate according to one or more of claims 1 to 8, characterized in that the chemical group and the aryl residue together correspond to one of the formulas F1-F11

10. The conjugate consisting of a) a polynucleotide, oligonucleotide or mononucleotide and b) one or more aryl residues of the formula (I), where the aryl residue (aryl residues) is either directly through a chemical bond or indirectly linked through a chemical group to 5 the 'end and / or 3'-end and / or one or more nucleoside bases, and / or one or more sugar residues, and / or one or more internucleoside bonds, and the chemical group is not a CH ₂ -S group if binding occurs through h internucleotide phosphodiester bond. 11. A method of obtaining a conjugate containing a transportable molecule and at least one aryl residue, which consists in the fact that a) a transportable molecule is obtained that contains a reactive functional group at the position to which the aryl residue is to be bound; b) receive an aryl a residue, and c) the transported molecule is reacted with an aryl residue to form a conjugate. 12. The method according to claim 11, characterized in that the reactive functional group is an amino group, a mercapto group, a chloroacetyl group, an isocyanate group, an isothiocyanate group, a carboxyl group, an N-hydroxysuccinimide group or a carboxylic acid chloride group. 13. The method according to one or more of claims 11 and 12, characterized in that the interaction of the transported molecule with an aryl residue is carried out at a pH value of ≤ 7.5. 14. The method according to one or more of claims 11 to 13, characterized in that the interaction of the transported molecule with an aryl residue is carried out at a pH of about 7.0. 15. The method according to one or more of claims 11-14, characterized in that the transported molecule is a polynucleotide, oligonucleotide or mononucleotide. 16. The use of an aryl residue of formula (I) or formula (II) associated with a transported molecule, for the transport of this molecule through a biological membrane. 17. A method of transporting a molecule through a membrane, which is that a) a conjugate is obtained in which the transported molecule is bound to at least one aryl residue of formula (I) or formula (II), and b) the conjugate is incubated with the membrane. 18. A method of transporting a molecule into a cell, the method comprising: a) obtaining a conjugate in which the transported molecule is bound to at least one aryl residue of the formulas (I) or (II), b) the conjugate is incubated with the cell, after which c) the conjugate is transported into the cell without cleavage of the aryl residue. 19. The method according to p, characterized in that the cell is a eukaryotic or prokaryotic cell. 20. The method according to one or more of claims 18 and 19, wherein the cell is a bacterial cell, a yeast cell or a mammalian cell. 21. The method according to one or more of claims 18 to 20, characterized in that the cell is a human cell. 22. The method according to one or more of claims 18 to 21, characterized in that the cell is a tumor cell. 23. A method for producing a medicinal product, which consists in the fact that a) a pharmaceutical biologically active substance or its derivative is obtained which contains at least one reactive functional group in the position to which the aryl residue is to be bound; b) an aryl residue is obtained of formula (I) or formula (II), c) a pharmaceutically active substance or its derivative is reacted with this aryl residue to form a conjugate, and d) if necessary, mix the conjugate t with other additives and / or carriers. 24. A medicine containing a conjugate according to one or more of claims 1 to 10. 25. A diagnostic tool containing the conjugate according to one or more of claims 1 to 10. 26. A test kit containing a conjugate according to one or more of claims 1 to 10.