title: Differential inhibition of DNA/protein interactions by aromatic amidines with 2, 3 and 4 benzamidine residues.
abstract: We have recently reported that aromatic polyamidines are powerful inhibitors of in vitro proliferation of tumour cell lines and in vivo tumorigenicity of melanoma cells xenografted into nude mice. Interestingly, we have found that tetrabenzamidines are able to bind DNA, and to inhibit the interaction between transacting factors and specific target DNA sequences. 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 target sequence of EBV DNA, containing the 12 bp palindromic consensus TAGCATATGCTA. The results obtained suggest that aromatic polyamidines inhibit the interactions between DNA-binding proteins and target DNA sequences with different efficiency, depending (i) on the number of amidine residues and (ii) on the presence of halogen substitutions (Cl, Br or I) on the benzene rings of tetra-benzamidine molecules.
authors.affiliation: Laboratorio Immunologia, Istituto Regina Elena, Roma, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Feriotto
authors.forename: C
authors.initials: C
authors.lastname: Nastruzzi
authors.forename: R
authors.initials: R
authors.lastname: Cortesi
authors.forename: A
authors.initials: A
authors.lastname: Ciucci
authors.forename: C
authors.initials: C
authors.lastname: Mischiati
authors.forename: R
authors.initials: R
authors.lastname: Gambari
mesh_terms: D000578:Amidines / Q000494:pharmacology*; D000956:Antigens, Viral / Q000378:metabolism*; D001483:Base Sequence; D001550:Benzamidines / Q000494:pharmacology*; D004247:DNA / Q000187:drug effects* / Q000378:metabolism*; D016172:DNA Fingerprinting; D004268:DNA-Binding Proteins / Q000378:metabolism*; D019309:Epstein-Barr Virus Nuclear Antigens; D008969:Molecular Sequence Data; D009841:Oligonucleotides / Q000378:metabolism; D011083:Polycyclic Compounds / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000378:metabolism; D016329:Sp1 Transcription Factor / Q000378:metabolism; D013329:Structure-Activity Relationship; D015534:Trans-Activators / Q000378:metabolism
chemical_list: D000578:Amidines; D000956:Antigens, Viral; D001550:Benzamidines; D004268:DNA-Binding Proteins; D019309:Epstein-Barr Virus Nuclear Antigens; D009841:Oligonucleotides; D011083:Polycyclic Compounds; D011994:Recombinant Proteins; D016329:Sp1 Transcription Factor; D015534:Trans-Activators; C057885:1,3-di-(4-amidinophenoxy)-2,2-bis-(4-amidinophenoxymethyl)propane; D004247:DNA