engleski

Interactions of bis-urea bridged bis-phenanthridines with DNA and RNA

Low weight organic molecules interacting with DNA and/or RNA are of continuously high scientific interest.1 Our recent results have pointed out that selectivity of bis-phenanthridinium derivatives toward various DNA/RNA sequences could be controlled by the steric effects2 or by electrostatic (pH controlled) interactions with DNA/RNA backbone and/or nucleobases.3 Since urea-containing aromatics have shown many biologically interesting features, 4 we have introduced two urea moieties into the linkers connecting phenanthridines with the idea that urea could offer recognition of various DNA/RNA sequences by hydrogen bonding. Fig. 1. Synthesized bis-urea bridged bis-phenanthridines 4-6. Changes in fluorescence spectrum of 6 (c=1.0×10-6 mol dm-3, pH=5): A) upon titration with ct-DNA ; B) upon titration with poly A- poly U. Novel bis-phenanthridine derivatives bridged by bis-urea linkers of variable length (Fig. 1) were synthesized and spectroscopicaly characterized. Spectroscopic study (UV/vis, fluorescence) revealed that interactions of 4-6 with DNA and RNA are strongly dependent on the length of the linker, as well as on the polynucleotide basepair constitution and DNA/RNA secondary structure. In addition, 6 could be considered as a specific fluorescence probe for poly A – poly U (Fig. 1B, strong fluorescence increase) and poly dA-poly dT, since addition of ct-DNA (Fig. 1A) and poly G – poly C results in quenching of 6 fluorescence. References (1) Demeunynck, M. ; Bailly C. ; Wilson, W.D. ; DNA and RNA binders, Wiley-VCH, Weinheim, 2002. (2) Piantanida, I. ; Palm, B.S. ; Čudić, P. ; Žinić, M. ; Schneider ; H.-J. Tetrahedron, 2004, 60, 6225. (3) Malojčić, G. ; Piantanida, I. ; Marinić, M. ; Žinić, M. ; Marjanović, M. ; Kralj, M. ; Pavelić K. ; Schneider ; H.-J. ; Org. Biomol. Chem., 2005, 3, 4373. (4) Kim, S.K. et al Tetrahedron, 2005, 61, 4545. ; Shipps, GW et al, Proc. Natl. Acad. Sci. USA, 1997, 94, 11833. ; Luedtke, N.W. et al, Bioorg. Med. Chem, 2003, 11, 5235. ; Mertz, E. et al, Bioorg. Med. Chem. 2004, 12, 1517.

bis-urea phenanthridine; DNA-RNA selectivity; intercalation;

nije evidentirano