Effects of anticancer drugs on transcription factor-DNA interactions.
DNA-interacting anticancer drugs are able to affect the propensity of DNA to interact with proteins through either reversible binding or covalent bond formation. The effect of the drugs on transcription factor interactions with DNA is reviewed. These effects can be classified as (i) competition between a drug and regulatory protein for target sequences; (ii) weakening of this interaction; (iii) enhancement of this interaction by chemical modification of the DNA and the creation of non-natural binding sites; and (iv) a 'suicide' mechanism, which is observed when a transcription factor induces changes in DNA structure, allowing a drug to bind to a target sequence. Several new strategies -- the antigene approach with oligonucleotides, peptide nucleic acids or locked nucleic acids, and sequence-specific polyamides -- are also reviewed.
Gniazdowski
Marek
M
Department of Medicinal Chemistry, Institute of Physiology and Biochemistry, Medical University of Lódz, Mazowiecka 6/8, 92-215 Lódz, Poland. magn@csk.am.lodz.pl
Denny
William A
WA
Nelson
Stephanie M
SM
Czyz
Malgorzata
M
D000970:Antineoplastic Agents / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D014157:Transcription Factors / Q000378:metabolism*
D000970:Antineoplastic Agents; D014157:Transcription Factors; D004247:DNA