Charge Migration Through Duplex Dna

DNA sequences containing contiguous AA or TT mismatches, as well as sequences containing a 3-deazacytidine analogue were synthesized. Irradiation of anthraquinone abstracts an electron from the DNA. The loss of an electron from double-stranded DNA results in the formation of a radical cation that migrates through the DNA where it reacts irreversibly with H2O or O2 at GG steps. Subsequent treatment with piperidine or Fpg enzyme cleaves the backbone of the DNA at the site of reaction. DNA oligomers were designed to contain contiguous AA, TT, or G3-deazacytidine mismatches. It was revealed that the mismatches destabilize the duplex DNA; however, there is no measurable effect on the overall secondary structure of the DNA. The contiguous (AA)n mismatch, where n 7, was shown to have no effect on charge migration efficiency. In contrast, the contiguous (TT)n mismatch, where n 2, was shown to have near complete inhibition of charge migration through the mismatch region. Charge migration through the G3-deazacytidine mismatch was shown to have no effect on charge migration efficiency as well. Interestingly, reaction at the (G3-deazacytidine)2 base pairs revealed a change in the ratio of oxidative damage at the Gs. In (GC)2 base pairs, the ratio of damage at the two Gs is 10:1 with the majority of damage occurring at the 5-G. However, the (G3-deazacytidine)2 base pairs had an equal distribution of damage at the 5 and 3-Gs, with the amount of total reactivity equaling the (GC)2 base pairs. These findings indicate that the base composition in mismatched DNA determines the effect on charge migration efficiency and trapping reactivity.

Charge migration through DNA has been the focus of considerable interest in recent years. This book presents contributions from an international team of researchers active in this field. It contains a wide range of topics that includes the mathematical background of the quantum processes involved, the role of charge transfer in DNA radiation damage, a new approach to DNA sequencing, DNA photonics, and many others.

The past few years have witnessed intense research in this fascinating field as well as many controversial discussions. Now the time is ripe for a comprehensive book covering not only theoretical aspects, but also such mechanistic topics as principles and mechanisms of photoinduced charge injection, transport and trapping in DNA, sequence-dependent DNA dynamics, spectroscopic investigations of hole transport and much more. From the contents: * Principles and Mechanisms of Photoinduced Charge Injection, Transport and Trapping in DNA * Sequence-Dependent DNA Dynamics: The Regulator of DNA-Mediated Charge Transport * Excess Electron Transfer in DNA Probed with Flavin and Thymine Dimer Modified Oligonucleotides * Dynamics of Photoinitiated Hole and Electron Injection in Duplex DNA * Spectroscopic Investigation of Oxidative Hole Transfer via Adenine Hopping in DNA * Chemical Probing of Reductive Electron Transfer in DNA * Chemical Approach for Modulating Hole Transport in DNA * Spectroscopic Investigation of Charge Transfer in DNA * Spectroscopic Probing of Ultrafast Structural Relaxation and Electron Transfer Dynamics in DNA Edited by Hans-Achim Wagenknecht, and written by renowned international authors, this book provides an excellent overview with high quality contributions, making it a "must-have" for everyone working in the field.

DNA is the carrier of biological information and damage to DNA has been believed to be responsible for many diseases including aging and cancer. One electron oxidation by charge migration through DNA is one of the processes that lead to DNA damage. It is known that the guanine N1 imino proton can be transferred to the N3 of cytidine that is hydrogen bonded to it. Some reports have implication that this proton transfer and radical cation migration are coupled to each other. We have incorporated 5-fluoro-2'-deoxycytidine (F5dC) in place of normal dC in DNA duplexes. Although, the lower pKa of F5dC should perturb the proton transfer process from the guanine to it, we do not see any change in the charge migration ability compared to the strands having normal cytidines. However, there is a considerable decrease in the guanine damage, when there is F5dC opposite to it. These results indicate that the charge migration is not coupled with proton transfer process, but the change in basicity affects the reactivity of the guanine radical cation. We have also reported a systematic study on the charge migration through adenine (A) and thymidine (T) containing DNA strands. The damage has predominantly seen in thymidine, although from oxidation potentials reaction at adenine was expected. The thymidine reaction has been analyzed thoroughly. It has similar distance dependence property as the well known guanine damage. Study of thymidine damage in presence of radical scavengers, replacement of thymidines by Uracil and HPLC-MS study point toward reactions involving tandem lesion. On the basis of these information and molecular modeling study we have proposed a possible pathway leading to one-electron oxidation at the thymidines.

with contributions by numerous experts

Frontiers in Computational Chemistry, originally published by Bentham and now distributed by Elsevier, presents the latest research findings and methods in the diverse field of computational chemistry, focusing on molecular modeling techniques used in drug discovery and the drug development process. This includes computer-aided molecular design, drug discovery and development, lead generation, lead optimization, database management, computer and molecular graphics, and the development of new computational methods or efficient algorithms for the simulation of chemical phenomena including analyses of biological activity. In Volume 2, the authors continue the compendium with nine additional perspectives in the application of computational methods towards drug design. This volume covers an array of subjects from modern hardware advances that accelerate new antibacterial peptide identification, electronic structure methods that explain how singlet oxygen damages DNA, to QSAR model validation, the application of DFT and DFRT methods on understanding the action of nitrogen mustards, the design of novel prodrugs using molecular mechanics and molecular orbital methods, computational simulations of lipid bilayers, high throughput screening methods, and more. Brings together a wide range of research into a single collection to help researchers keep up with new methods Uniquely focuses on computational chemistry approaches that can accelerate drug design Makes a solid connection between experiment and computation, and the novel application of computational methods in the fields of biology, chemistry, biochemistry, physics, and biophysics

The free-radical chemistry of DNA had been discussed in some detail in 1987 in my book The Chemical Basis of Radiation Biology. Obviously, the more recent developments and the concomitant higher level of understanding of mechanistic details are missing. Moreover, in the living cell, free-radical DNA damage is not only induced by ionizing radiation, but free-radical-induced DNA damage is a much more general phenomenon. It was, therefore, felt that it is now timely to review our present knowledge of free-radical-induced DNA damage induced by all conceivable free-radical-generating sources. Originally, it had been thought to include also a very important aspect, the repair of DNA damage by the cell’s various repair enzymes. Kevin Prise (Cancer Campaign, Gray Laboratory, L- don) was so kind to agree to write this part. However, an adequate description of this strongly expanding area would have exceeded the allocated space by much, and this section had to be omitted. The directors of the Max-Planck-Institut für Strahlenchemie (now MPI für Bioanorganische Chemie), Karl Wieghardt and Wolfgang Lubitz, kindly allowed me to continue to use its facilities after my retirement in 2001. Notably, our - brarian, Mrs. Jutta Theurich, and her right-hand help, Mrs. Rosemarie Schr- er, were most helpful in getting hold of the literature. I thank them very much. Without their constant help, this would have been very difficult indeed.

This is the most updated, comprehensive collection of monographs on all aspects of photochemistry and photophysics related to natural and synthetic, inorganic, organic, and biological supramolecular systems. Supramolecular Photochemistry: Controlling Photochemical Processes addresses reactions in crystals, organized assemblies, monolayers, zeolites, clays, silica, micelles, polymers, dendrimers, organic hosts, supramolecular structures, organic glass, proteins and DNA, and applications of photosystems in confined media. This landmark publication describes the past, present, and future of this growing interdisciplinary area.

A series of anthraquinone-linked DNA oligonucleotides was prepared and the efficiency of long-distance radical cation migration was measured. In one set of oligonucleotides, two GG steps are separated by either a TATA or an ATAT bridge. In these two compounds, the efficiency of radical cation migration from GG to GG differs by more than an order of magnitude. Replacement of the thymines in the TATA or ATAT bridges with 3-methyl-2-pyridone (t, a thymine analog) results in the much more efficient radical cation migration across the bridge in both cases. This is attributed to a decrease in the oxidation potential of t to a value below that of A. In contrast, replacement of the thymines in the TATA or ATAT bridges with difluorotoluene (f, a thymine analog with high oxidation potential) does not measurably affect radical cation migration. These findings are readily accommodated by the phonon-assisted polaron-hopping mechanism for long-distance charge transfer in duplex DNA and indicate that DNA in solution behaves as a polaronic semiconductor. Oligomers containing thiophene-pyrrole-thiphene (SNS) monomers were covalently linked to the nucleobases of DNA. Treatment of these oligomers with horseradish peroxidase and hydrogen peroxide lead to the formation of conducting oligomers conjoined to the DNA. The DNA template aligns the oligomers along one strand of the duplex and limits the intermolecular reaction of monomers. This method enables utilization of the unique self-recognizing properties and programmability of DNA to create tailored oligomers.