Binding specificity of post-activated neocarzinostatin chromophore drug-bulged DNA complex studied using electrospray ionization mass spectrometry

J Mass Spectrom. 1996 Jan;31(1):31-6. doi: 10.1002/(SICI)1096-9888(199601)31:1<31::AID-JMS244>3.0.CO;2-I.

Abstract

Electrospray ionization mass spectrometry (ESI-MS) was employed to characterize the binding specificity of a bulged 22-mer DNA hairpin with a post-activated neocarzinostatin chromophore (NCS-Chrom) having two similar forms, where 2a has an H in a location for which 2b has it replaced by a CH2OH group. Specific binding of 2a to the bulged 22-mer DNA was observed whereas little binding was detected for 2a to non-bulged DNA 19-mer and 12-mer duplexes. The stoichiometry of the 22-mer DNA complex with 2a was determined to be predominantly 1:1. Substitution of hydrogen in 2a for the hydroxymethylene group in 2b dramatically reduced the binding strength to the 22-mer DNA. Little complex formation was observed for 2b and 22-mer DNA based upon the ESI-MS data, consistent with earlier fluorescence studies. The results indicate that ESI-MS can be a sensitive technique for probing conformational specificity in studies of biomolecular binding.

Publication types

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

MeSH terms

  • Antibiotics, Antineoplastic / metabolism*
  • Base Sequence
  • DNA / chemistry
  • DNA / metabolism*
  • Enediynes
  • Mass Spectrometry*
  • Molecular Sequence Data
  • Molecular Structure
  • Nucleic Acid Conformation
  • Zinostatin / analogs & derivatives
  • Zinostatin / chemistry
  • Zinostatin / metabolism

Substances

  • Antibiotics, Antineoplastic
  • Enediynes
  • neocarzinostatin chromophore
  • DNA
  • Zinostatin