Claims
- 1. A method for the delivery of an antisense oligodeoxynucleotide to cells, comprising the steps of,forming a complex comprising said oligodeoxynucleotide and a polynuclear platinum compound, and providing said complex to cells.
- 2. The method of claim 1 wherein said polynuclear platinum compound has the structural formula: wherein X, Y and Z are selected from the group consisting of: am(m)ines, mono-dentate diamines, aromatic planar amines, sulfoxides and leaving groups; A is selected from the group consisting of: NH2(CH2)bH2N, wherein b=2-12; NH2(CH2)bNR(CH2)cH2N, wherein b and c range from 2 to 12, and R is selected from the group consisting of: H2, (C1-C6 alkyl), (C1-C6)acyl, and (C1-C6)alkyloxycarbonyl; NH2(CH2)bNR(CH2)cNR(CH2)dH2N wherein b, c and d range from 2 to 12, and R is selected from the group consisting of: H2, (C1-C6 alkyl), (C1-C6)acyl, and (C1-C6)alkyloxycarbonyl); (NH2(CH2)bH2N)(NH2(CH2)cH2N)Pt(X)(Z) wherein b and c range from 2-12, and X and Z are selected from the group consisting of: am(m)ines, mono-dentate diamines, aromatic planar amines, sulfoxides and leaving groups; (NH2(CH2)bH2N)Pt(X)(Z)(NH2(CH2)cH2N)Pt(X)(Z)(NH2(CH2)dH2N) and wherein b, c and d range from 2-12, and X and Z are selected from the group consisting of: am(m)ines, mono-dentate diamines, aromatic planar amines, sulfoxides and leaving groups; (NH2(CH2)bH2N)Pt(X)(Z)(NH2(CH2)cH2N)Pt(X)(Z)(NH2(CH2)dH2N)Pt(X)(Z)(NH2(CH2)eH2N) wherein b, c, d, and e range from 2-12 and X and Z are selected from the group consisting of: am(m)ines, mono-dentate diamines, aromatic planar amines, sulfoxides and leaving groups; {(NH2(CH2)aH2N)(NH2(CH2)bH2N)M(L)4}m+ wherein a and b range from 2-12, M is a non-platinum metal, L is a ligand selected from the group consisting of: monodentate and bidentate chelates, and m+ is the charge on the non-platinum metal, and n+ is the charge on said polynuclear platinum compound.
- 3. The method of claim 1 wherein said polynuclear platinum compound has the structural formula: wherein A═NH2(CH2)bNR(CH2)cH2N where R═(CH2)dH2N and b, c and d range from 2 to 12; X, Y and Z are selected from the group consisting of: am(m)ines, mono-dentate diamines, aromatic planar amines, sulfoxides and leaving groups; and n+ represents the overall charge on said polynuclear platinum compound.
- 4. The method of claim 1 wherein said polynuclear platinum compound has the structural formula: wherein A═NH2(CH2)bNR1(CH2)cNR2(CH2)dH2N, where R1═(CH2)eH2N, R2═(CH2)fH2N and b, c, d, e and f range from 2 to 12; X, Y and Z are selected from the group consisting of: am(m)ines, mono-dentate diamines, aromatic planar amines, sulfoxides and leaving groups; and n+ represents the overall charge on said polynuclear platinum compound.
- 5. The method of claim 1 wherein said oligodeoxynucleotide is an unmodified phosphodiester oligodeoxynucleotide.
- 6. The method of claim 1 wherein said polynuclear platinum compound is 1,0,1/t,t,t n=6,6.
- 7. The method of claim 1 wherein said polynuclear platinum compound is a structural derivative of 1,0,1/t,t,t n=6,6.
- 8. The method of claim 7 wherein said structural derivative of 1,0,1/t,t,t n=6,6 is 0,0,0/t,t,t n=6,6.
- 9. A method for the treatment of cancer in a patient in need thereof, comprising the steps of:forming a complex comprising an oligodeoxynucleotide and a polynuclear platinum compound, wherein said polynuclear platinum compound is selected from the group consisting of 1,0,1/t,t,t n=6,6 and a structural derivative of 1,0,1/t,t,t n=6,6 and administering said complex to said patient.
- 10. The method of claim 9 wherein said polynuclear platinum compound is 1,0,1/t,t,t n=6,6.
- 11. The method of claim 9 wherein said polynuclear platinum compound is a structural derivative of 1,0,1/t,t,t n=6,6.
- 12. The method of claim 11 wherein said structural derivative of 1,0,1/t,t,t n=6,6 is 0,0,0/t,t,t n=6,6.
- 13. The method of claim 9 wherein the sequence of said oligodeoxynucleotide is SEQ ID NO: 1.
- 14. A composition comprisinga single-stranded oligodeoxynucleotide, and a polynuclear platinum compound complexed with said single-stranded oligodeoxynucleotide wherein said polynuclear platinum compound is selected on the group consisting of i) a polynuclear platinum compound having the structural formula: wherein X, Y and Z are selected from the group consisting of: am(m)ines, mono-dentate diamines, aromatic planar amines, sulfoxides and leaving groups; A is selected from the group consisting of: NH2(CH2)bH2N, wherein b=2-12 NH2(CH2)bNR(CH2)cH2N, wherein b and c range from 2 to 12, and R is selected from the group consisting of: H2, (C1-C6 alkyl), (C1-C6)acyl, and (C1-C6)alkyloxycarbonyl; NH2(CH2)bNR(CH2)cNR(CH2)dH2N wherein b, c and d range from 2 to 12, and R is selected from the group consisting of: H2, (C1-C6 alkyl), (C1-C6)acyl, and (C1-C6)alkyloxycarbonyl); (NH2(CH2)bH2N)(NH2(CH2)cH2N)Pt(X)(Z) wherein b and c range from 2-12, and X and Z are selected from the group consisting of: am(m)ines, mono-dentate diamines, aromatic planar amines, sulfoxides and leaving groups; (NH2(CH2)bH2N)Pt(X)(Z)(NH2(CH2)cH2N)Pt(X)(Z)(NH2(CH2)dH2N) and wherein b, c and d range from 2-12, and X and Z are selected from the group consisting of: am(m)ines, mono-dentate diamines, aromatic planar amines, sulfoxides and leaving groups; (NH2(CH2)bH2N)Pt(X)(Z)(NH2(CH2)cH2N)Pt(X)(Z)(NH2(CH2)dH2N)Pt(X)(Z)(NH2(CH2)eH2N) wherein b, c, d, and e range from 2-12 and X and Z are selected from the group consisting of: am(m)ines, mono-dentate diamines, aromatic planar amines, and sulfoxides; {(NH2(CH2)aH2N)(NH2(CH2)bH2N)M(L)4}m+ wherein a and b range from 2-12, M is a non-platinum metal, L is a ligand selected from the group consisting of: monodentate and bidentate chelates, and m+ is a charge on the non-platinum metal, and n+ is a charge on said polynuclear platinum compound; ii) a polynuclear platinum compound having the structural formula: wherein A═NH2(CH2)bNR(CH2)cH7N where R═(CH2)dH2N and b, c and d range from 2 to 12; X, Y and Z are selected from the group consisting of; am(m)ines, mono-dentate diamines, aromatic planar amines, sulfoxides and leaving groups; and n+ represents an overall charge on said polynuclear platinum compound; and iii) a polynuclear platinum compound having the structural formula: wherein A═NH2(CH2)bNR1(CH2)cNRc(CH2)dH2N, where R1═(CH2)cH2N, R2═(CH2)fH2N and b, c, d, e and f range from 2 to and 12; X, Y and Z are selected from the group consisting of: am(m)ines, mono-dentate diamines, aromatic planar amines, sulfoxides and leaving groups; and n+ represents an overall charge on said polynuclear platinum compound.
- 15. The composition of claim 14 wherein said polynuclear platinum compound is complexed with said single-stranded oligodeoxynucleotide by covalent bonds.
- 16. The composition of claim 14 wherein said polynuclear platinum compound is complexed with said single-stranded oligodeoxynucleotide by electrostatic bonds.
- 17. The composition of claim 14 wherein said polynuclear platinum compound is selected from the group consisting of: 1,0,1/t,t,t n=6,6 and 0,0,0/t,t,t n=6,6.
- 18. A polynuclear platinum compound having the structural formula: wherein X, Y and Z are selected from the group consisting of: am(m)ines, mono-dentate diamines, aromatic planar amines, sulfoxides and leaving groups; A is selected from the group consisting of: NH2(CH2)bNR(CH2)cH2N, wherein b and c range from 2 to 12, and R is selected from the group consisting of: H2, (C1-C6 alkyl), (C1-C6)acyl, and (C1-C6)alkyloxycarbonyl; NH2(CH2)bNR(CH2)cNR(CH2)dH2N wherein b, c and d range from 2 to 12, and R is selected from the group consisting of: H2, (C1-C6 alkyl), (C1-C6)acyl, and (C1-C6)alkyloxycarbonyl); (NH2(CH2)bH2N)(NH2(CH2)cH2N)Pt(X)(Z) wherein b and c range from 2-12, and X and Z are selected from the group consisting of: am(m)ines, mono-dentate diamines, aromatic planar amines, sulfoxides; (NH2(CH2)bH2N)Pt(X)(Z)(NH2(CH2)cH2N)Pt(X)(Z)(NH2(CH2)dH2N) and wherein b, c and d are sulfoxides; (NH2(CH2)bH2N)Pt(X)(Z)(NH2(CH2)cH2N)Pt(X)(Z)(NH2(CH2)dH2N) Pt(X)(Z)(NH2(CH2)eH2N) wherein b, c, d, and e range from 2-12 and X and Z are sulfoxides; {(NH2(CH2)aH2N)(NH2(CH2)bH2N)M(L)4}m+ wherein a and b range from 2-12, M is a non-platinum metal, L is a ligand selected from the group consisting of: monodentate and bidentate chelates, and m+ is the charge on the non-platinum metal, and n+ is the charge on said polynuclear platinum compound.
- 19. A polynuclear platinum compound having the structural formula: wherein A═NH2(CH2)bNR(CH2)cH2N where R═(CH2)dH2N and b, c and d range from 2 to 12; X, Y and Z are selected from the group consisting of: am(m)ines, mono-dentate diamines, aromatic planar amines, sulfoxides; and n+ represents the overall charge on said polynuclear platinum compound.
- 20. A polynuclear platinum compound having the structural formula wherein A═NH2(CH2)bNR1(CH2)cNR2(CH2)dH2N, where R1═(CH2)eH2N, R2═(CH2)fH2N and b, c, d, e and f range from 2 to 12; X, Y and Z are selected from the group consisting of: am(m)ines, monodentate diamines, aromatic planar amines, sulfoxides and leaving groups; and n+ represents an overall charge on said polynuclear platinum compound.
Government Interests
This invention was made using funds from grants from the National Institutes of Health having grant number 1RO1-CA78754-01. The government may have certain rights in this invention.
Non-Patent Literature Citations (2)
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