N1-SUBSTITUTED TETRA-BENZAMIDINES - INHIBITION OF DNA-PROTEIN INTERACTIONS AND INVITRO TUMOR-CELL GROWTH
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- Published online on: August 1, 1992 https://doi.org/10.3892/ijo.1.3.277
- Pages: 277-281
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Abstract
The pharmacological-mediated inhibition of the interaction between regulatory proteins and target DNA sequences could represent a potential experimental strategy to control growth of neoplastic cells, viral DNA replication and biological life cycle of infectious microorganisms. Aromatic polyamidines are powerful inhibitors of DNA-protein interactions, in vitro proliferation of tumor cell lines and in vivo growth of tumorigenic cells xenografted into nude mice. In order to obtain more detailed information on structure-activity relationships, we have analysed the effects of different aromatic polyamidines on the binding of a recombinant protein, the Epstein-Barr Virus (EBV) Nuclear Antigen 1 (EBNA-1) to the DNA target sequence of EBV, containing the 12 bp palindromic consensus TAGCATATGCTA sequence. The results obtained suggest that aromatic polyamidines differentially inhibit the interactions between DNA-binding proteins and target DNA sequences, leading to differential effects on tumor cell growth.