A homo-oligonucleotide of between 2 and 26 monomers of 5-fluorouridine 5'-monophosphate or 5-fluorodeoxyuridine 5'-monophosphate covalently linked via 3'- to 5'-phosphodiester linkages, where at the 3'- or 5'- terminus there is covalently linked a molecule selected from the group consisting of cholesterol, ethyl-spaced adamatane, 1,2-di-hexadecylglycerol and poly-L-lysine. These homo-oligonucleotides exhibit antitumor activity.
Novel compounds comprising 5-fluorouracil or 5-fluorouridine covalently linked to 5-ethynyluracil, 5-ethynyluridine or 5-propynyluracil and pharmaceutical compositions comprising such compounds are disclosed.
Disclosed is a composition including an oligonucleotide complexed with a cyclodextrin. The oligonucleotide may be noncovalently associated with the cyclodextrin. Alternatively, the oligonucleotide may be covalently complexed with adamantane which is noncovalently associated with the cyclodextrin. Also disclosed are methods of enhancing the cellular uptake and intracellular concentration of oligonucleotides, methods of increasing the solubility of an oligonucleotide in a cell, and methods of treating a cell for viral infection or to prevent viral infection.
Disclosed is a composition including an oligonucleotide complexed with a cyclodextrin. The oligonucleotide may be noncovalently associated with the cyclodextrin. Alternatively, the oligonucleotide may be covalently complexed with adamantane which is noncovalently associated with the cyclodextrin. Also disclosed are methods of enhancing the cellular uptake and intracellular concentration of oligonucleotides, methods of increasing the solubility of an oligonucleotide in a cell, and methods of treating a cell for viral infection or to prevent viral infection.
Disclosed is a composition including an oligonucleotide complexed with a cyclodextrin. The oligonucleotide may be noncovalently associated with the cyclodextrin. Alternatively, the oligonucleotide may be covalently complexed with adamantane which is noncovalently associated with the cyclodextrin. Also disclosed are methods of enhancing the cellular uptake and intracellular concentration of oligonucleotides, methods of increasing the solubility of an oligonucleotide in a cell, and methods of treating a cell for viral infection or to prevent viral infection.
A method for treating neoplastic disease in animals including humans comprises administering a first composition comprising a TS inhibitor and a second composition comprising a nucleic acid-directed chemotherapeutic agent, and a composition for treating neoplastic disease in animals including humans comprises a first composition comprising a TS inhibitor and a second composition comprising a nucleic acid-directed chemotherapeutic agent. In a preferred embodiments, the TS inhibitor is a homo-oligomer of FdUMP, and the nucleic acid-directed chemotherapeutic agent is 5-FU or a pro-drug thereof. In a further aspect, compositions of a homo-oligonucleotide of 5-fluoro-2'-deoxyuridine-5'-O-monophosphate (FdUMP) with 5-fluorouracil exhibit a synergistic biological effect on neoplastic cells when compared to the activity of the individual components, the compositions being useful in the treatment of cancer in animals, including humans.
