NMR investigation of the binding of the anticancer drug actinomycin D to oligodeoxyribonucleotides with isolated 5'd(GC)3' binding sites
Imino proton and /sup 31/P NMR studies were conducted on the binding of actinomycin D (ActD) to self-complementary oligodeoxyribonucleotides with one GC binding site (d(ATATGCATAT) (1), d(ATACGCGTAT) (2), and d(ATATACGCGTATAT) (3)) and with two GC sites (d(ATGCATGCAT) (4)). At R = 1 (molar ratio of ActD to oligomer duplex) ActD caused a doubling of the number of imino proton signals at, and adjacent to, the GC binding site of 1. One of the G-C base pair signals shifted upfield while the other shifted downfield. Both of the signals for the A-T base pairs adjacent to the binding site shifted downfield. All imino proton signals of 2 and the longer sequence, 3 shifted upfield on binding of ActD to the GC site, indicating a sequence-dependent change in base stacking on complex formation. For both 1 and 2 addition of ActD resulted in a similar pattern of three downfield /sup 31/P NMR signals. The two most downfield signals have chemical shift and temperature dependence which are characteristic of phosphate groups at isolated intercalation sites. At R = 1 the ActD complex with 4 has very complex spectra with both upfield and downfield A-T and G-C imino signals. All these data were consistent with two 1:1 complexes with the unsymmetrical phenoxazone ring adopting both of the two possible orientations. The variety of ActD adducts observed for these relatively simple sequences indicates that ActD binding to natural DNA must be much more complex than previously anticipated.
- Research Organization:
- Georgia State Univ., Atlanta (USA)
- OSTI ID:
- 7001631
- Journal Information:
- Biochemistry; (United States), Journal Name: Biochemistry; (United States) Vol. 27:16; ISSN BICHA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
62 RADIOLOGY AND NUCLEAR MEDICINE
ACTINOMYCIN
ADDUCTS
AMINES
AMINO ACIDS
ANTI-INFECTIVE AGENTS
ANTIBIOTICS
ANTIMITOTIC DRUGS
ANTINEOPLASTIC DRUGS
AROMATICS
AZAARENES
AZINES
CARBOXYLIC ACIDS
CHELATING AGENTS
CHEMICAL SHIFT
CYTOSINE
DEUTERIUM COMPOUNDS
DNA ADDUCTS
DRUGS
EDTA
GUANINE
HETEROCYCLIC COMPOUNDS
HYDROGEN COMPOUNDS
HYDROXY COMPOUNDS
ISOTOPES
LIGANDS
LIGHT NUCLEI
MAGNETIC RESONANCE
MOLECULAR BIOLOGY
NUCLEAR MAGNETIC RESONANCE
NUCLEI
NUCLEIC ACIDS
ODD-EVEN NUCLEI
OLIGONUCLEOTIDES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
OVERHAUSER EFFECT
PHOSPHORUS 31
PHOSPHORUS ISOTOPES
PURINES
PYRIMIDINES
RESONANCE
STABLE ISOTOPES