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- Title
Chemistry and biology of DNA-binding small molecules.
- Authors
Paul, Ananya; Bhattacharya, Santanu
- Abstract
Regulation of the transcription machinery is one of the many ways to achieve control of gene expression. This has been done either at the transcription initiation stage or at the elongation stage. Different methodologies are known to inhibit transcription initiation via targeting of double-stranded (ds) DNA by: (i) synthetic oligonucleotides, (ii) ds-DNA-specific, sequenceselective minor-groove binders (distamycin A), intercalators (daunomycin) combilexins and (iii) small molecule (peptide or intercalator)-oligonucleotide conjugates. In some cases, instead of ds-DNA, higher order G-quadruplex structures are formed at the start site of transcription. In this regard G-quadruplex DNA-specific small molecules play a significant role towards inhibition of the transcription machinery. Different types of designer DNA-binding agents act as powerful sequence-specific gene modulators, by exerting their effect from transcription regulation to gene modification. But most of these chemotherapeutic agents have serious side effects. Accordingly, there is always a challenge to design such DNA-binding molecules that should not only achieve maximum specific DNA-binding affinity, and cellular and nuclear transport activity, but also would not interfere with the functions of normal cells.
- Subjects
DNA-binding proteins; GENETIC transcription; GENE expression; ELONGATION factors (Biochemistry); OLIGONUCLEOTIDE synthesis; DISTAMYCIN; BIOCONJUGATES; TRANSPORT theory
- Publication
Current Science (00113891), 2012, Vol 102, Issue 2, p212
- ISSN
0011-3891
- Publication type
Article