/sup 1/H and /sup 31/P NMR investigations of actinomycin D binding selectivity with oligodeoxyribonucleotides containing multiple adjacent d(GC) sites
Imino proton and /sup 31/P NMR studies were conducted on the binding of actinomycin D (ActD) to self-complementary oligodeoxyribonucleotides with adjacent 5'-GC-3' sites. ActD showed very high specificity for binding to GC sites regardless of oligomer length and surrounding sequence. For a first class of duplexes with a central GCGC sequence, a mixture of 1:1 complexes was observed due to the two different orientations of the ActD phenoxazone ring system. Analysis of /sup 1/H chemical shifts suggested that the favored 1:1 complex had the benzenoid side of the phenoxazone ring over the G base in the central base pair of the GCGC sequence. This is the first case in which an unsymmetrical intercalator has been shown to bind to DNA in both possible orientations. A unique 2:1 complex, with significantly different /sup 1/H and /sup 31/P chemical shifts relative to those of the 1:1 complexes, was formed with these same oligomers, again with the benzenoid side of the ActD molecule over the G base of the central GC base pair. There is considerable anticooperativity to binding of the second ActD in a GCGC sequence. Both upfield and downfield shifts were seen for imino proton signals for base pairs adjacent to ActD binding sites. This suggests that ActD has considerable long-range effects on oligomer conformation. Anticooperativity was also seen in NMR studies with a second class of oligomers containing alternating GC sequences longer than GCGC. It was found that in any three consecutive GC binding sites only two ActD can be bound. Anticooperativity can, thus, define the apparent number of base pairs in the binding site of a intercalator. Binding results with poly(d(G-C)) x poly(d(G-C)) were similar to those obtained with an oligomer containing four consecutive GC sites.
- Research Organization:
- Georgia State Univ., Atlanta (USA)
- OSTI ID:
- 5271410
- Journal Information:
- Biochemistry; (United States), Journal Name: Biochemistry; (United States) Vol. 27:3; ISSN BICHA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
62 RADIOLOGY AND NUCLEAR MEDICINE
ACTINOMYCIN
ANTI-INFECTIVE AGENTS
ANTIBIOTICS
ANTIMITOTIC DRUGS
ANTINEOPLASTIC DRUGS
BARYONS
CHEMICAL SHIFT
CONFIGURATION INTERACTION
DRUGS
ELEMENTARY PARTICLES
FERMIONS
HADRONS
HEAVY WATER
HYDROGEN COMPOUNDS
ISOTOPES
LIGHT NUCLEI
MAGNETIC RESONANCE
NUCLEAR MAGNETIC RESONANCE
NUCLEI
NUCLEIC ACIDS
NUCLEONS
ODD-EVEN NUCLEI
OLIGONUCLEOTIDES
ORGANIC COMPOUNDS
OXYGEN COMPOUNDS
PHOSPHORUS 31
PHOSPHORUS ISOTOPES
PROTON SPECTRA
PROTONS
RESONANCE
SPECTRA
STABLE ISOTOPES
WATER