Molecular Basis of Specificity in Nucleic Acid-Drug Interactions: Proceedings of the Twenty-Third Jerusalem Symposium on Quantum Chemistry and Biochem

ISBN-13: 9789401056571 / Angielski / Miękka / 2012 / 603 str.

A. Pullman; Joshua Jortner

Opis

One of the central problems in the study of the mechanism of DNA-ligand interactions is the existence and nature of sequence specificity with respect to the base pairs of DNA. The presence of such a specificity could be of particular significance because it might possibly mean the involvement of specific genes in the effectiveness of the different drugs. The elucidation of the factors responsible for the specificity could then be important for the development of compounds susceptible to contribute to the control of gene expression and also to the development of rationally conceived, improved new generations of effective and specific chemotherapeutic agents. Important recent achievements, experimental and theoretical, in the analysis of such sequence specificities open prospects for possible rapid progress in this field. The 23rd Jerusalem symposium was devoted to the exploration of these recent achievements in relation to many types of ligand, with special emphasis on antitumor drugs. All major types of interaction, intercalation, groove binding, covalent linking, coordination, have been considered. So was also the effect of the interaction on the structure and properties of the nucleic acids and the relationship between the interaction and biological or pharmacological activities. We feel that this Volume presents a relatively complete up-to-date account of the state of the art in this important field of research.

Spis treści

Mutual Conformational Adaptation of Both Ligand and Receptor in Antitumor Drug-DNA Complexes.- DNA Drug Interactions studied with Polarized Light Spectroscopy : the DAPI Case.- Drug-DNA Recognition : Sequence Specificity of the DNA Minor Groove Binder Berenil.- Binding of Minor Groove Ligands to Short DNA Segments : Berenil Complexed with d(GCAATTGC)2 and d(GCTTAAGC)2.- The Sequence Specificity of Damage Caused by [125I]-Labelled Hoechst 33258 and UV/IodoHoechst 33258 in Intact Cells and in Cloned Sequences of Purified DNA which differ by a Small Number of Base Substitutions.- Structure and Dynamics of a [1:1] Drug-DNA Complex : Analysis of 2D NMR Data Using Molecular Mechanics and Molecular Dynamics Calculations.- Determination of Distamycin-A Binding Modes by NMR.- Molecular Mechanisms of DNA Sequence Recognition by Groove Binding Ligands : Biochemical and Biological Consequences.- Daunomycin Binding to DNA : from the Macroscopic to the Microscopic.- In Vitro Transcription Analysis of the Sequence Specificity of Reversible and Irreversible Complexes of Adriamycin with DNA.- Quantitative Footprinting Analysis of the Actiomycin D-DNA Interaction.- Structural Requirements for DNA Topoisomerase II Inhibition by Anthracyclines.- Thermodynamic Studies of Amsacrine Antitumor Agents with Nucleic Acids.- Kinetic and Equilibrium Binding Studies of a Series of Intercalating Agents that Bind by Threading a Sidechain Through the DNA Helix.- Aminoacyl-Anthraquinones : DNA-Binding and Sequence Specificity.- The Molecular Basis of Specific Recognition Between Echinomycin and DNA.- Bis-Pyrrolecarboxamides Linked to Intercalating Chromophore Oxazolopyridocarbazole (OPC) : Properties Related to the Selective Binding to DNA at Rich Sequences.- Parallel-Stranded Nucleic Acids and their Interaction with Intercalating and Groove Binding Drugs.- Design of Bifunctional Nucleic Acid Ligands.- Sequence-Specific Recognition and CLeavage of Duplex DNA by Derivatized Oligonucleotides.- Bis(Platinum) Complexes. Chemistry, Antitumor Activity and DNA-Binding.- Interaction of Calicheamicin with DNA.- The Effects of Ligand Structure on Binding Mode and Specificity in the Interaction of Unfused Aromatic Cations with DNA.- Modulation of Protein-DNA Interactions by Intercalating and Nonintercalating Agents.- Antitumor Antibiotics Endowed with DNA Sequence Specificity.- Cationic Porphyrin-DNA Complexes : Specificity of Binding Modes.- Complementary Studies on Sequence Specificity in DNA-Antitumor Drugs Interactions.- Uranyl Photofootpring. DNA Structural Changes upon Binding of Mithramycin.- Characteristics of Noncovalent and Covalent Interactions of (+) and (-) Anti-Benzo[a]pyrene Diol Epoxide Stereoisomers of Different Biological Activities with DNA.- Aflatoxin-DNA Binding and the Characterization of Aflatoxin B1-Oligodeoxynucleotide Adducts by 1H NMR Spectroscopy.- Sequence Specific Isotope Effects on the Cleavage of DNA by Radical-Generating Drugs.- Quinolone-DNA Interaction : How a Small Drug Molecule Acquires High DNA Binding Affinity and Specificity.- Mechanisms of DNA Sequence Selective Modifications by Alkylating Agents.- Contrasting Mechanisms for the Sequence Recognition of DNA by(+)- and (-)-CC-1065.- Course of Recognition and Covalent Reactions Between Mitomycin C and DNA : Sequence Selectivity of a Cross-Linking Drug.- Triplex Forming Oligonucleotide Reagents : Rationalization of DNA Site Selectivity and Application in a Pharmaceutical Context.- Experimental Proofs of a Drug’s DNA Specificity.