NMR studies of the interaction of chromomycin A/sub 3/ with small DNA duplexes
/sup 1/H and /sup 31/P NMR spectral analysis of a chromomycin/d(ATGCAT)/sub 2/ complex provides strong evidence for a nonintercalative mode of drug binding. Investigation of the imino proton region of the duplex suggests a protection of one of the two guanine imino protons from fast exchange with the bulk water up to at least 45 /sup 0/C by the drug. Subsequent one-dimensional nuclear Overhauser enhancement experiments place the exchangeable chromomycin chromophoric hydroxyl proton <0.45 nm from this guanine imino proton and the chromophore 7-methyl <0.45 from the internal thymine 6-proton and/or the guanine 8-proton. /sup 1/H two-dimensional NMR reveals that the duplex retains a right-handed B conformation but there are distortions at the TGC region of one chain and large deviations in the chemical shift of protons relative to the uncomplexed duplex in the other chain in the same TGC region. The data suggest that the chromomycin chromophore is oriented such that the hydrophilic side of the ring system is proximal the helix center in the major groove near the TG region while the aromatic side of the ring is oriented away from the helix but is partially protected from the solvent by the aliphatic chain, which bends back over the two aromatic protons. Changes in the /sup 32/P spectrum of the duplex on binding of the drug are different from the effect of either actinomycin or netropsin on nucleic acid fragments.
- Research Organization:
- Univ. of California, San Francisco
- OSTI ID:
- 6522228
- Journal Information:
- Biochemistry; (United States), Journal Name: Biochemistry; (United States) Vol. 26:4; ISSN BICHA
- Country of Publication:
- United States
- Language:
- English
Similar Records
Kinetics for exchange of the imino protons of the d(C-G-C-G-A-A-T-T-C-G-C-G) double helix in complexes with the antibiotics netropsin and/or actinomycin
Solution structure of the chromomycin-DNA complex
Related Subjects
62 RADIOLOGY AND NUCLEAR MEDICINE
AMINES
ANTI-INFECTIVE AGENTS
ANTIBIOTICS
AROMATICS
AZAARENES
BARYONS
CONFIGURATION INTERACTION
DNA
DRUGS
ELEMENTARY PARTICLES
FERMIONS
GUANINE
HADRONS
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
ISOTOPES
LIGHT NUCLEI
MAGNETIC RESONANCE
NUCLEAR MAGNETIC RESONANCE
NUCLEI
NUCLEIC ACIDS
NUCLEONS
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
OVERHAUSER EFFECT
PHOSPHORUS 31
PHOSPHORUS ISOTOPES
PROTONS
PURINES
RESONANCE
STABLE ISOTOPES