NITROGEN-15-LABELED OLIGODEOXYNUCLEOTIDES .6. USE OF N-15 NMR TO PROBE BINDING OF NETROPSIN AND DISTAMYCIN TO (D[CGCGAATTCGCG])2

The binding of netropsin and distamycin to the duplex {d[CGCGAATTCGCG] }2, in which adenine residues A5 or A6 were [3-N-15] labeled, was moni tored by N-15 NMR to probe the sensitivity of these N-15 labels to dru g binding. The N-15 chemical shifts were obtained from a H-1-N-15 hete ronuclear 2D experiment. The N-15 atoms in the asymmetric complexes we re assigned with use of, in addition, a H-1-H-1 2D NOESY experiment. T he results for both complexes show that water is excluded from the cen ter of the binding site, and that there is hydrogen bonding to the N3 at the common propylamidinium termini of the drugs. Further, in the di stamycin complex, there is a second drug.H bond at the formamide termi nus of the drug. These results demonstrate that these N-15 labels are useful monitors of drug binding.