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.

[1]  I. Tinoco,et al.  Kinetics for exchange of imino protons in the d(C-G-C-G-A-A-T-T-C-G-C-G) double helix and in two similar helices that contain a G . T base pair, d(C-G-T-G-A-A-T-T-C-G-C-G), and an extra adenine, d(C-G-C-A-G-A-A-T-T-C-G-C-G). , 1982, Biochemistry.

[2]  I. Tinoco,et al.  Kinetics for exchange of imino protons in deoxyribonucleic acid, ribonucleic acid, and hybrid oligonucleotide helices. , 1982, Biochemistry.

[3]  D. Patel,et al.  DNA conformation, dynamics, and interactions in solution. , 1982, Science.

[4]  D. Patel,et al.  Premelting and melting transitions in the d(CGCGAATTCGCG) self-complementary duplex in solution. , 1982, Biochemistry.

[5]  D. Patel,et al.  Mutual interaction between adjacent dG . dC actinomycin binding sites and dA . dT netropsin binding sites on the self-complementary d(C-G-C-G-A-A-T-T-C-G-C-G) duplex in solution. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[6]  H R Drew,et al.  Structure of a B-DNA dodecamer. III. Geometry of hydration. , 1981, Journal of molecular biology.

[7]  P. D. Johnston,et al.  Study of transfer ribonucleic acid unfolding by dynamic nuclear magnetic resonance. , 1981, Biochemistry.

[8]  R. Wells,et al.  A 300- and 600-MHz proton nuclear magnetic resonance investigation of a 12 base pair deoxyribonucleic acid restriction fragment: relaxation behavior of the low-field resonances in water. , 1981, Biochemistry.

[9]  J. Feigon,et al.  Direct measurement of spin-spin and spin-lattice relaxation rates of exchangeable NH protons of DNA in water , 1980 .

[10]  Richard E. Dickerson,et al.  Crystal structure analysis of a complete turn of B-DNA , 1980, Nature.

[11]  D. Patel.  Nuclear magnetic resonance studies of drug-nucleic acid interactions at the synthetic DNA level in solution , 1979 .

[12]  T. Krugh,et al.  Proton magnetic resonance studies of actinomycin D complexes with mixtures of nucleotides as models for the binding of the drug to DNA. , 1977, Biochemistry.

[13]  D. Crothers,et al.  Kinetic studies of drug-dinucleotide complexes. , 1976, Biochemistry.

[14]  A. Redfield,et al.  Dynamic range in Fourier transform proton magnetic resonance , 1975 .

[15]  D. Crothers,et al.  DNA-ethidium reaction kinetics: demonstration of direct ligand transfer between DNA binding sites. , 1975, Journal of molecular biology.

[16]  R. Wells,et al.  Netropsin. A specific probe for A-T regions of duplex deoxyribonucleic acid. , 1974, The Journal of biological chemistry.

[17]  W. A. Sexton,et al.  STRUCTURE—ACTIVITY RELATIONSHIPS , 1958, The Journal of pharmacy and pharmacology.

[18]  C. Zimmer.  Effects of the antibiotics netropsin and distamycin A on the structure and function of nucleic acids. , 1975, Progress in nucleic acid research and molecular biology.