Antitumor drug nogalamycin binds DNA in both grooves simultaneously: Molecular structure of nogalamycin-DNA complex
- Univ. of Illinois, Urbana-Champaign (USA)
- Leiden State Univ. (Netherlands)
The three-dimensional molecular structures of the complexes between an interesting antitumor drug, nogalamycin, and two DNA hexamers, d(CGT(pS)ACG) and d(m{sup 5}CGT(pS)Am{sup 5}CG), were determined at high resolution by X-ray diffraction analyses. Two nogalamycins bind to the DNA double helix in a 2:1 ratio with the aglycon chromophore intercalated between the CpG steps at both ends of the helix. The nogalose and aminoglucose sugars lie in the minor and major grooves, respectively, of the distorted B-DNA double helix. The binding of nogalamycin to DNA requires that the base pairs in DNA open up transiently to allow the bulky sugars to go through. Specific hydrogen bonds are found in the complex between the drug and guanine bases. The authors suggest that nogalamycin may prefer GC sequences embedded in a stretch of AT sequences.
- OSTI ID:
- 6920519
- Journal Information:
- Biochemistry; (USA), Vol. 28:26; ISSN 0006-2960
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
ANTINEOPLASTIC DRUGS
CROSS-LINKING
DNA
X-RAY DIFFRACTION
OLIGONUCLEOTIDES
ANTIBIOTICS
CHEMICAL BONDS
COMPLEXES
CYTOSINE
DNA SEQUENCING
GUANINE
MOLECULAR STRUCTURE
STEREOCHEMISTRY
AMINES
ANTI-INFECTIVE AGENTS
AROMATICS
AZAARENES
AZINES
CHEMICAL REACTIONS
COHERENT SCATTERING
DIFFRACTION
DRUGS
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
POLYMERIZATION
PURINES
PYRIMIDINES
SCATTERING
STRUCTURAL CHEMICAL ANALYSIS
550602* - Medicine- External Radiation in Diagnostics- (1980-)