INTERACTION OF DISTAMYCIN A AND NETROPSIN WITH QUADRUPLEX AND DUPLEX STRUCTURES: A COMPARATIVE ¹H-NMR STUDY

ABSTRACT

Homonuclear NMR techniques have been used to investigate the interactions of the minor groove binding agents distamycin A (Dist-A) and the related drug netropsin (Net) with three quadruplexes characterized by different groove widths: [d(TGGGGT)]₄ (Q1), [d(GGGGTTTTGGGG)]₂ (Q2), and d(GGGGTTGGGGTGTGGGGTTGGGG) (Q3). Netropsin has been found to be in a fast chemical exchange with all three kinds of quadruplexes, whereas Dist-A interacts tightly with Q1 and, at a less extent, with Q2. In order to determine the degree of selectivity of Dist-A for two- rather than four-stranded DNA, we titrated with Dist-A an equimolar solution of Q1 and the duplex d(CGCAAATTTGCG)₂ (D). This comparative ¹H-NMR study allowed us to conclude that Dist-A and, consequently, Net possess higher affinity for duplex DNA.

ACKNOWLEDGMENTS

This work is supported by Italian M.U.R.S.T. (P.R.I.N. 2001). The authors are grateful to “Centro Ricerche Interdipartimentale di Analisi Strumentale,” C.R.I.A.S., for supplying NMR facilities. Gilda Minichini and Ester Del Pezzo are acknowledged for their kind collaboration.