Solution conformation of the antitumor antibiotic chromomycin A/sub 3/ determined by two-dimensional NMR spectroscopy

Journal Article · Tue May 17 04:00:00 EDT 1988 · Biochemistry; (United States)

OSTI ID:7026710

Kam, M; Shafer, R H; Berman, E

A conformational analysis and a complete assignment of the nonexchangeable proton resonances of chromomycin A/sub 3/, dechromose-A chromomycin A/sub 3/, and deacetylchromose-B chromomycin A/sub 3/ were carried out in organic solvents. The resulting conformation in methanol has the three side chains of chromomycin A/sub 3/ fully extended, away from one another and from the aglycon. In dichloromethane on the other hand, the drug was shown to adopt a highly compact conformation in which most of the 26 oxygen atoms in the molecule point out toward the solvent. The two carbohydrate side chains extend parallel to each other on the same side of the aglycon. Two intramolecular nuclear Overhauser enhancement contacts have been observed between different sugar units on these side chains, indicating close proximity for these moieties. In addition, the aliphatic side chain is folded toward the aglycon, parallel to the two oligosaccharide side chains. The overall conformation has a wedge-like shape with the two phenoxy groups exposed at the pointed edge. The presence of some exchange cross-peaks in the NOESY spectra suggests the presence of intramolecular hydrogen bonds that probably help to maintain the compact information. The derivatives of chromomycin A/sub 3/ have qualitatively similar conformations, though their respective conformations are not as compact as the parent drug. The significance of these results is discussed in terms of a model of chromomycin A/sub 3/ binding to DNA in the major groove.

• Research Organization: Weizmann Institute of Science, Rehovot (Israel)
• OSTI ID: 7026710
• Journal Information: Biochemistry; (United States), Journal Name: Biochemistry; (United States) Vol. 27:10; ISSN BICHA
• 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 SHIFT
CHROMATOGRAPHY
CONFIGURATION INTERACTION
DNA
DRUGS
ELEMENTARY PARTICLES
FERMIONS
HADRONS
MAGNETIC RESONANCE
NUCLEAR MAGNETIC RESONANCE
NUCLEIC ACIDS
NUCLEONS
ORGANIC COMPOUNDS
OVERHAUSER EFFECT
PROTONS
RESONANCE
SEPARATION PROCESSES
THIN-LAYER CHROMATOGRAPHY