Unstable Hoogsteen base pairs adjacent to echinomycin binding sites within a DNA duplex

Journal Article · Mon May 01 00:00:00 EDT 1989 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.86.9.3006· OSTI ID:5442373

Gilbert, D E; van der Marel, G A; van Boom, J H; Feigon, J ^[1]

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1. Univ. of California, Los Angeles (USA)

The bisintercalation complex present between the DNA octamer (d(ACGTACGT)){sub 2} and the cyclic octadepsipeptide antibiotic echinomycin has been studied by one- and two-dimensional proton NMR, and the results obtained have been compared with the crystal structures of related DNA-echinomycin complexes. Two echinomycins are found to bind cooperatively to each DNA duplex at the CpG steps, with the two quinoxaline rings of each echinomycin bisintercalating between the C{center dot}G and A{center dot}T base pairs. At low temperatures, the A{center dot}T base pairs on either side of the intercalation site adopt the Hoogsteen conformation, as observed in the crystal structures. However, as the temperature is raised, the Hoogsteen base pairs in the interior of the duplex are destabilized and are observed to be exchanging between the Hoogsteen base pair and either an open or a Watson-Crick base-paired state. The terminal A{center dot}T base pairs, which are not as constrained by the helix as the internal base pairs, remain stably Hoogsteen base-paired up to at least 45{degree}C. The implications of these results for the biological role of Hoogsteen base pairs in echinomycin-DNA complexes in vivo are discussed.

• OSTI ID: 5442373
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (USA) Vol. 86:9; ISSN PNASA; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

550601* -- Medicine-- Unsealed Radionuclides in Diagnostics
62 RADIOLOGY AND NUCLEAR MEDICINE
ANTI-INFECTIVE AGENTS
ANTIBIOTICS
BARYONS
CHEMICAL REACTIONS
CHEMICAL SHIFT
CROSS-LINKING
DNA
DRUGS
ELEMENTARY PARTICLES
FERMIONS
HADRONS
MAGNETIC RESONANCE
NMR SPECTRA
NUCLEAR MAGNETIC RESONANCE
NUCLEIC ACIDS
NUCLEONS
OLIGONUCLEOTIDES
ORGANIC COMPOUNDS
OVERHAUSER EFFECT
POLYMERIZATION
PROTONS
RESONANCE
SPECTRA