INTERACTION OF NOVEL GUANIDINIOCARBONYL-
-PYRROLES WITH DNA/RNA POLYNUCLEOTIDES

Radić Stojković, M., Zagreb/HR, Klemm, K., Essen/D, Piantanida, I., Zagreb/HR Schmuck, C., Essen/D
Marijana Radić Stojković, Ruđer Bošković Institute, PO Box 180, 10002, Zagreb

Recent studies of aryl-guanidiniocarbonyl-pyrrole conjugates revealed several interesting interactions with DNA/RNA. Some were able to differentiate between ds‑DNA and ds-RNA by several spectroscopic methods,1,2 while others recognized different basepair composition of polynucleotides.1

Figure 1. Polycationic, DNA/RNA active guanidiniocarbonyl-pyrrole conjugates.

Interactions of novel, water-soluble guanidiniocarbonyl-pyrroles such as 1-3 with nucleic acids, have been studied by UV-Vis spectroscopy, circular dichroism and thermal denaturation experiments at pH = 7.0 and pH = 5.0. Binding constants Ks and ratios n[bound compound]/[DNA/RNA] obtained by processing of UV/Vis titration data with Scatchard equation revealed similar affinity toward ds-DNA and ds-RNA. The exception was hexacationic pyrrole derivative 3 which has a higher affinity toward poly dA ‑ poly dT in comparison to the other two compounds. 
Thermal stabilization of poly A - poly U, poly dA - poly dT and poly (dA-dT)2 duplexes upon addition of pyrrole derivatives was significantly higher at pH = 5 than at neutral conditions, which was consistent with the number of positive charges of studied compounds. The addition of pyrrole derivatives to polynucleotide solutions in most cases resulted in an increase of  CD signals of the polynucleotides in the 260‑300 nm region and very strong positive induced (ICD) bands at >300 nm.
Those results suggest that dominant interaction occurs within minor groove of polynucleotide, most likely as a result of a combination of hydrogen bonding and electrostatic interaction between guanidinium groups of the pyrrole derivatives and the polynucleotide backbone and/or base pairs.

[1] L. Hernandez-Folgado, D. Baretić, I. Piantanida, M. Marjanović, M. Kralj, T. Rehm, C. Schmuck, Chemistry, Eur. J. 2010, DOI: 10.1002/chem.200901999.
[2] L. Hernandez-Folgado, C. Schmuck, S. Tomić, I. Piantanida, Bioorg. Med. Chem. Lett. 2008, 18, 2977.