BINDING OF DELTA-[RU(PHEN)(3)](2-[RU(PHEN)(3)](2+) TO [D(CGCGATCGCG)](2) STUDIED BY NMR() AND LAMBDA)

The interactions of the Delta and Delta enantiomers of the chiral meta l complex [Ru(phen)(3)](2+) (phen = 1,10-phenanthroline) with the olig onucleotide duplex [d(CGCGATCGCG)](2) have been studied with NMR and C D spectroscopy. From NOESY data it is shown that the interaction prima rily takes place in the minor groove of the oligonucleotide which rema ins in a B-like conformation. The observed NOEs also provide evidence that the metal complexes preferentially bind to the central AT region. The observed AT specificity is more pronounced with the Delta as comp ared to the Delta enantiomer, which interacts with a larger part of th e oligonucleotide. Furthermore, the NOESY data show that neither of th e enantiomers binds by classical intercalation. This is also supported by a comparison study of the analogue [Ru(phen)(2)DPPZ](2+) (DPPZ = d ipyrido[ 3,2-a:2',3'-c] phenazine) which intercalates in DNA. The NMR as well as the CD results show that the Delta and Delta enantiomers of [Ru(phen)(3)](2+) bind in different modes to [d(CGCGATCGCG)](2). Comp arison of CD spectra of the metal complex in the presence of [d(CGCGAT CGCG)](2), poly(dAdT).poly(dAdT), poly(dGdC).poly(dGdC), and calf thym us DNA suggests that these binding modes are independent of DNA sequen ce. The results are found to be compatible with binding of Delta-[Ru(p hen)(3)](2+) by insertion of two phenanthroline ligands into the minor groove, causing minor distortions of the DNA structure, whereas the D elta enantiomer binds in a mode that leaves the DNA structure unaffect ed.