engleski

Recognition of various DNA / RNA sequences by 4, 9-diazapyrenium and bis-phenanthridinium derivatives in aqueous media

Small molecules that base their biological activity on DNA/RNA interactions are of special interest because they can more easily cross biological membranes than large molecules, and can even be delivered to cells strongly resistant to exogenous matter. Among DNA/RNA binding molecules, those that intercalate into DNA/RNA are intensively studied as novel fluorescent markers for nucleic acids, molecular tools, or simply due to broad spectra of their biological activities.1b Very recently, even thoroughly studied molecules as classical DNA/RNA intercalator ethidium bromide (EB) had to be re-evaluated, since it became obvious that mechanisms of non-covalent interactions are not completely understood. Recent reports pointed out versatility of the phenanthridinium core, 2a, , including even intriguing biological activity. Among main focuses of our research are bis-ethidium bromide (EB) derivatives (Fig. 1.) including 4, 9-diazapyrenium cations (4, 9-DAPs ; Fig. 2.), which are mimicking EB with extended aromatic surface. The recent results, which would be presented in this lecture, show that 4, 9-DAPs reveal dramatically different physico-chemical properties, among which the pH dependent opening of the heteroaromatic ring is the most prominent and should be stressed as the possible cause of the observed selectivity toward tumor cell lines. The 4, 9-DAPs intercalate into double stranded and single stranded DNA and RNA, their affinity and specificity being strongly dependent on the attached substituents, as well as their antitumour activity.6, Furthermore, our recent results pointed out that selectivity of bis-phenanthridinium derivatives toward various DNA/RNA sequences could be controlled by the steric effects or by electrostatic (hydrogen bonding, pH controlled) interactions with DNA/RNA backbone and/or nucleobases. All aforementioned stressed versatility of the phenanthridinium core for preparation of novel biologically intriguing small organic compounds

phenanthridine; diazapyrene; DNA; RNA

nije evidentirano