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Int J Oncol. 1992 Aug;1(3):277-81.

N1-substituted tetra-benzamidines - inhibition of DNA-protein interactions and invitro tumor-cell growth.

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  • 1UNIV FERRARA,IST CHIM BIOL,VIA L BORSARI N46,I-44100 FERRARA,ITALY. UNIV FERRARA,DIPARTIMENTO SCI FARMACEUT,I-44100 FERRARA,ITALY. CTR INTERDIPARTIMENTALE BIOTECNOL,I-44100 FERRARA,ITALY.

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.

PMID:
21584542
[PubMed]
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