Oligodeoxyribonucleotides comprising O.sup.6 -benzylguanine and their use
US6060458A · kind A · utility
Assignees
Inventors
Key dates
| Filing date | Feb 13, 1998 |
| Grant date | May 9, 2000 |
| Priority date | — |
| Expiry date | Feb 13, 2018 |
Classification
- Technology area (CPC A)Human Necessities
- CPC primaryA61P43/00
- WIPO fieldPharmaceuticals
- WIPO sectorChemistry
Abstract
The present invention provides a single-stranded oligodeoxyribonucleotide, which (i) comprises from about 5 to 11 bases, at least one of which is a substituted or an unsubstituted O.sup.6 -benzylguanine, and (ii) inactivates human AGT. The present invention also provides a single-stranded oligodeoxyribonucleotide, which can inactivate a mutant human AGT, which either is not inactivated by O.sup.6 -benzylguanine or is less inactivated by O.sup.6 -benzylguanine than by said single-stranded oligodeoxyribonucleotide. A phosphate of the single-stranded oligodeoxyribonucleotide can be replaced by a methylphosphonate or a phosphorothioate. The present invention also provides a composition comprising such an oligodeoxyribonucleotide. In addition, the present invention provides a method of enhancing the effect of an antineoplastic alkylating agent, which alkylates the O.sup.6 position of guanine residues in DNA, in the chemotherapeutic treatment of cancer in a mammal, which method comprises the co-administration to the mammal of a cancer-treatment effective amount of an antineoplastic alkylating agent and a chemotherapeutic treatment-enhancing amount of a present inventive oligodeoxyribonuc…
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