Kinetics for exchange of the imino protons of the d(C-G-C-G-A-A-T-T-C-G-C-G) double helix in complexes with the antibiotics netropsin and/or actinomycin
The lifetimes for exchange of the imino protons in the dodecanucleotide d(C-G-C-G-A-A-T-T-C-G-C-G) upon binding of netropsin and/or actinomycin have been measured by proton nuclear magnetic resonance experiments. At high temperature these lifetimes were found to measure the lifetimes for opening of the base pairs in the double helix. Comparison of the opening rates in the dodecamer with those in the complex with netropsin (which binds at the -A-A-T-T- sequence) shows that there is not only a large kinetic stabilization of the A-T base pairs at the binding site but also a significant stabilization of the G-C base pairs adjacent to the netropsin binding site. For the complex with actinomycin, which intercalates at the G-C sites in the double strand, the lifetimes of the base pairs at the binding site increase upon binding of actinomycin, and the A-T base pairs in the central core are slightly kinetically destabilized by the actinomycin binding. The activation energies for exchange of the imino protons were also measured in the complexes and indicate that the mechanism for exchange of the imino protons is individual base-pair opening, where one base pair opens independently of the others. The effects of drug binding on the dynamics of individual base pairs in a double-stranded helix are discussed.
- Research Organization:
- Univ. of California, Berkeley
- DOE Contract Number:
- AC03-76SF00098
- OSTI ID:
- 5745223
- Journal Information:
- Biochemistry; (United States), Journal Name: Biochemistry; (United States) Vol. 22:5; ISSN BICHA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
59 BASIC BIOLOGICAL SCIENCES
ACTINOMYCIN
ACTIVATION ENERGY
ANTI-INFECTIVE AGENTS
ANTIBIOTICS
ANTIMITOTIC DRUGS
ANTINEOPLASTIC DRUGS
BARYONS
BIOCHEMICAL REACTION KINETICS
CHARGED-PARTICLE TRANSPORT
CHEMICAL BONDS
COMPLEXES
CONFIGURATION
DNA
DRUGS
ELEMENTARY PARTICLES
ENERGY
FERMIONS
HADRONS
HELICAL CONFIGURATION
KINETICS
LIFETIME
MAGNETIC RESONANCE
NUCLEAR MAGNETIC RESONANCE
NUCLEIC ACIDS
NUCLEONS
NUCLEOTIDES
ORGANIC COMPOUNDS
PROTON TRANSPORT
PROTONS
RADIATION TRANSPORT
REACTION KINETICS
RESONANCE