Nucleic acid intercalating agents
AssigneeGenentech, Inc.
InventorsNorbert W. Bischofberger, Mark D. Matteucci
Life of this patent
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Abstract
Pyridinone or pyrimidinone nucleoside bases containing fused aromatic polycyclic rings are provided. These polycyclic nucleosides are incorporated into oligonucleotides and hybridized to complementary nucleic acid. Fluorescence spectroscopy and thermal denaturation profiles provided evidence that the polycyclic base is intercalated into the resulting duplex. The fused polycyclic ring systems optionally are substituted with reactive species which inactivate complementary nucleic acids. The oligonucleotides of this invention are useful as improved probes, diagnostic reagents, or for cleaving or derivatizing predetermined domains within nucleic acids.
Claims19
A pyridinone or pyrimidinone nucleoside comprising a fused aromatic polycyclic base having molecular dimensions equal to or less than about 30-50 angstroms by about 30-50 angstroms by about 3-7 angstroms, wherein the nucleoside is represented by the structure ##STR18## wherein R.sub.3 is an aromatic polycycle comprising up to four fused aromatic rings;
- Y is C or N;
- R.sub.7 is N or .dbd.C(R.sub.1)--;
- R.sub.1 and R.sub.6 are independently selected from the group consisting of H, halogen, C.sub.1 -C.sub.10 -alkyl, saturated or unsaturated cycloalkyl, C.sub.1 -C.sub.10 -alkylcarbonyloxy, C.sub.1 -C.sub.10 -alkyl, hydroxy-C.sub.1 -C.sub.10 -alkyl, heterocycle (N,O, or S), and nitro and;
- R.sub.2 is a ribose or deoxyribose sugar.
An oligonucleotide of the structure:
- ##STR20## wherein A is an insoluble matrix or the nucleoside ##STR21## R.sub.5 is H or hydroxyl;
- R.sub.4 is O, S, alkyl, alkylamine, or alkyl ether;
- n is an integer;
- and B is a nucleoside base;
- wherein at least one base is of the structure;
- ##STR22## and is positioned within about the first 20 percent or about the last 20 percent of the length of the oligonucleotide, and wherein
- R.sub.3 is the residue of an aromatic polycycle;
- Y is C or N;
- R.sub.7 is N or .dbd.C(R.sub.1)--;
- R.sub.1 and R.sub.6 are independently selected from the group consisting of hydrogen, halogen, C.sub.1 -C.sub.10 -alkoxy, saturated or unsaturated cycloalkyl, C.sub.1 -C.sub.10 -alkylcarbonyloxy, C.sub.1 -C.sub.10 -alkyl, hydroxy-C.sub.1 -C.sub.10 -alkyl, heterocycle (N,O,S), and nitro.
Dependencies are inferred from the claim text.