Sequence specificity of quinoxaline antibiotics. 2. NMR studies of the binding of [N-MeCys3,N-MeCys7]TANDEM and triostin A to DNA containing a CpI step.

The binding of CysMeTANDEM and triostin A to DNA containing a CpI step has been studied by one- and two-dimensional H-1 NMR spectroscopy. CysMeTANDEM binds sequence specifically to CpI steps as well as TpA steps as a bis-intercalator with the peptide backbone in the minor groove of the DNA. Only nonspecific, nonintercalative binding is observed between triostin A and DNA containing a CpI step. Comparison of the CysMeTANDEM-[d(GGACITCC)](2) complex to the CysMeTANDEM-[d(GGATATCC)](2) complex indicates that the structures of both complexes are very similar. However, CysMeTANDEM binds less tightly to [d(GGACITCC)](2) than to [d(GGATATCC)](2). The NMR evidence presented provides molecular insight into the role of stacking interactions and hydrogen bonding between the drug and the DNA in the sequence-specific binding of CysMeTANDEM to TpA sites and of triostin A to CpG sites.