Solution structure of the chromomycin-DNA complex

Journal Article · Mon Jan 23 23:00:00 EST 1989 · Biochemistry; (USA)

DOI:https://doi.org/10.1021/bi00428a051· OSTI ID:5563018

Gao, X; Patel, D J ^[1]

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1. Columbia Univ., New York, NY (USA)

The structure of the chromomycin-DNA complex at the deoxyoctanucleotide duplex level has been determined from one- and two-dimensional proton NMR studies in Mg-containing aqueous solution. The NMR results demonstrate that the antitumor agent binds as a symmetrical dimer to the self-complementary d(T-T-G-G-C-C-A-A) duplex with retention of the 2-fold symmetry in the complex. A set of intermolecular nuclear Overhauser enhancements (NOEs) established that two chromomycin molecules in the dimer share the minor groove at the G-G-C-C{center dot}G-G-C-C segment in such a way that each hydrophilic edge of the chromophore is located next to the G-G{center dot}C-C half-site and each C-D-E trisaccharide chain extends toward the 3{prime}-direction of the octanucleotide duplex. In addition, the A-B disaccharide segment and the hydrophilic side chain of the antitumor agent are directed toward the phosphate backbone. The observed changes in nucleic acid NOEs and coupling patterns on complex formation establish a transition to a wider and shallower minor groove at the central G-G-C-C{center dot}G-G-C-C segment required for accommodating the chromomycin dimer. The present demonstration that chromomycin binds as a dimer and switches the conformation of the DNA at its G{center dot}C-rich minor groove binding site provides new insights into antitumor agent design and the sequence specificity of antitumor agent-DNA recognition.

• OSTI ID: 5563018
• Journal Information: Biochemistry; (USA), Journal Name: Biochemistry; (USA) Vol. 28:2; ISSN 0006-2960; ISSN BICHA
• Country of Publication: United States
• Language: English

Related Subjects

550601* -- Medicine-- Unsealed Radionuclides in Diagnostics
62 RADIOLOGY AND NUCLEAR MEDICINE
ANTINEOPLASTIC DRUGS
AQUEOUS SOLUTIONS
BARYONS
BIOSYNTHESIS
CHEMICAL REACTIONS
CHEMICAL SHIFT
CROSS-LINKING
DISPERSIONS
DNA
DRUGS
ELEMENTARY PARTICLES
FERMIONS
HADRONS
INHIBITION
MAGNETIC RESONANCE
MIXTURES
MOLECULAR STRUCTURE
NUCLEAR MAGNETIC RESONANCE
NUCLEIC ACIDS
NUCLEONS
ORGANIC COMPOUNDS
POLYMERIZATION
PROTONS
RESONANCE
RNA
SOLUTIONS
STEREOCHEMISTRY
SYNTHESIS