Dna-binding polymers
AssigneeCalifornia Institute of Technology
InventorsPeter B. Dervan, Shane Foister, Raymond Doss, Michael A. Marques
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Abstract
Methods and compositions are provided for forming complexes between dsDNA and novel DNA-binding polymers comprising N-terminal thiophene-containing moieties which exhibit selectivity for T-A base pairs. By appropriate choice of target sequences and DNA-binding polymers, complexes comprising polymer-DNA are obtained with high association constants. The formation of complexes can be used for identification of specific dsDNA sequences, for inhibiting gene transcription, and as a therapeutic for inhibiting proliferation of undesired cells or modulation of expression of specific genes.
Claims20
A method for modulating the expression of a gene, said method comprising:
- contacting said gene with an effective amount of a DNA-binding polymer under conditions such that said DNA-binding polymer binds to a double stranded portion of said gene, thereby modulating the expression of said gene, wherein said DNA binding polymer comprises:
- a first terminus,
- an oligomeric backbone optionally containing a linking element, and
- a second terminus;
- wherein:
- said first terminus is an optionally substituted thiophene-containing moiety;
- said oligomeric backbone comprises a plurality of optionally substituted monomer elements;
- said second terminus is selected from the group consisting of optionally substituted N-methylpyrrole, optionally substituted N-methylimidazole, and optionally substituted benzimidazole moiety;
- said DNA-binding polymer is effective to bind to a double-stranded DNA sequence having a number of DNA base pairs in the range (n/2) to (2n) where n is the number of monomer elements in said DNA-binding polymer;
- and
- said first terminus and said second terminus of said DNA-binding polymer are effective in combination to bind to a T-A DNA base pair.
A method for inhibiting transcription of a gene in an organism, said method comprising:
- administering to said organism an effective amount of one or more DNA-binding oligomers, selected so as to provide specific binding either singly or in pairs to a target double stranded DNA in a minor groove target site of said double stranded DNA, wherein said DNA-binding polymer comprises:
- a first terminus,
- an oligomeric backbone optionally containing a linking element, and
- a second terminus;
- wherein:
- said first terminus is an optionally substituted thiophene-containing moiety;
- said oligomeric backbone comprises a plurality of optionally substituted monomer elements;
- said second terminus is selected from the group consisting of optionally substituted N-methylpyrrole, optionally substituted N-methylimidazole, and optionally substituted benzimidazole moiety;
- said DNA-binding polymer is effective to bind to a double-stranded DNA sequence having a number of DNA base pairs in the range (n/2) to (2n) where n is the number of monomer elements in said DNA-binding polymer;
- and
- said first terminus and said second terminus of said DNA-binding polymer are effective in combination to bind to a T-A DNA base pair.
Dependencies are inferred from the claim text.