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 1H 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(GGA-TATCC)]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.
Addess
K J
KJ
Department of Chemistry and Biochemistry and Molecular Biology Institute, University of California, Los Angeles 90024-1569.
Feigon
J
J
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites; D002236:Carbohydrate Conformation; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011810:Quinoxalines / Q000737:chemistry / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D011810:Quinoxalines; C075619:(N-MeCys(3)-N-MeCys(7))TANDEM; C031945:triostin A; D004247:DNA