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

Biochemistry. 1994 Oct 18;33(41):12397-404. doi: 10.1021/bi00207a006.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / metabolism*
  • Base Sequence
  • Binding Sites
  • Carbohydrate Conformation
  • DNA / chemistry
  • DNA / metabolism*
  • Hydrogen Bonding
  • Magnetic Resonance Spectroscopy*
  • Models, Molecular
  • Molecular Sequence Data
  • Quinoxalines / chemistry
  • Quinoxalines / metabolism*

Substances

  • Anti-Bacterial Agents
  • Quinoxalines
  • (N-MeCys(3)-N-MeCys(7))TANDEM
  • triostin A
  • DNA