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.
Author(s): Andrew H.-J. Wang, Yen-Chywan Liaw (auth.), Bernard Pullman, Joshua Jortner (eds.)
Series: The Jerusalem Symposia on Quantum Chemistry and Biochemistry 23
Edition: 1
Publisher: Springer Netherlands
Year: 1990
Language: English
Pages: 603
Tags: Biochemistry, general; Medical Biochemistry
Front Matter....Pages i-x
Mutual Conformational Adaptation of Both Ligand and Receptor in Antitumor Drug-DNA Complexes....Pages 1-21
DNA Drug Interactions Studied with Polarized Light Spectroscopy: The DAPI Case....Pages 23-41
Drug-DNA Recognition: Sequence-Specificity of the DNA Minor Groove Binder Berenil....Pages 43-57
Binding of Minor Groove Ligands to Short DNA Segments: Berenil Complexed with d(GCAATTGC) 2 and d(GCTTAAGC) 2 ....Pages 59-65
The sequence specificity of damage caused by [ 125 I]-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....Pages 67-73
Structure and Dynamics of a [1:1] Drug-DNA Complex: Analysis of 2D NMR Data Using Molecular Mechanics and Molecular Dynamics Calculations....Pages 75-93
Determination of Distamycin-A Binding Modes by NMR....Pages 95-101
Molecular Mechanisms of DNA Sequence Recognition by Groove Binding Ligands: Biochemical and Biological Consequences....Pages 103-122
Daunomycin Binding to DNA: From the Macroscopic to the Microscopic....Pages 123-136
In Vitro Transcription Analysis of the Sequence Specificity of Reversible and Irreversible Complexes of Adriamycin with DNA....Pages 137-155
Quantitative Footprinting Analysis of the Actinomycin D-DNA Interaction....Pages 157-166
Structural Requirements for DNA Topoisomerase II Inhibition by Anthracyclines....Pages 167-176
Thermodynamic Studies of Amsacrine Antitumor Agents with Nucleic Acids....Pages 177-189
Kinetic and Equilibrium Binding Studies of a Series of Intercalating Agents That Bind by Threading a Sidechain through the DNA Helix....Pages 191-206
Aminoacyl-Anthraquinones: DNA-Binding and Sequence Specificity....Pages 207-224
The Molecular Basis of Specific Recognition between Echinomycin and DNA....Pages 225-245
Bis-Pyrrolecarboxamides Linked to Intercalating Chromophore Oxazolopyridocarbazole (OPC): Properties Related to the Selective Binding to DNA at Rich Sequences....Pages 247-260
Parallel-Stranded Nucleic Acids and Their Interaction with Intercalating and Groove Binding Drugs....Pages 261-274
Design of Bifunctional Nucleic Acid Ligands....Pages 275-290
Sequence-Specific Recognition and Cleavage of Duplex DNA by Derivatized Oligonucleotides....Pages 291-299
Bis(Platinum) Complexes. Chemistry, Antitumor Activity and DNA-Binding....Pages 301-321
Interaction of Calicheamicin with DNA....Pages 323-330
The Effects of Ligand Structure on Binding Mode and Specificity in the Interaction of Unfused Aromatic Cations with DNA....Pages 331-353
Modulation of Protein-DNA Interactions by Intercalating and Nonintercalating Agents....Pages 355-367
Antitumor Antibiotics Endowed with DNA Sequence Specificity....Pages 369-383
Cationic Porphyrin-DNA Complexes: Specificity of Binding Modes....Pages 385-399
Complementary Studies on Sequence Specificity in DNA-Antitumor Drugs Interactions....Pages 401-422
Uranyl Photofootprinting. DNA Structural Changes Upon Binding of Mithramycin....Pages 423-431
Characteristics of Noncovalent and Covalent Interactions of (+) and (-) Anti -Benzo[a]Pyrene Diol Epoxide Stereoisomers of Different Biological Activities with DNA....Pages 433-450
Aflatoxin-DNA Binding and the Characterization of Aflatoxin B 1 -Oligodeoxynucleotide Adducts by 1 H NMR Spectroscopy....Pages 451-480
Sequence Specific Isotope Effecfs on the Cleavage of DNA by Radical-Generating Drugs....Pages 481-493
Quinolone-DNA Interaction: How a Small Drug Molecule Acquires High DNA Binding Affinity and Specificity....Pages 495-512
Mechanisms of DNA Sequence Selective Modifications by Alkylating Agents....Pages 513-530
Contrasting Mechanisms for the Sequence Recognition of DNA by (+)- and (-)-CC-1065....Pages 531-550
Course of Recognition and Covalent Reactions between Mitomycin C and DNA: Sequence Selectivity of a Cross-Linking Drug....Pages 551-564
Triplex Forming Oligonucleotide Reagents: Rationalization of DNA Site Selectivity and Application in a Pharmaceutical Context....Pages 565-578
Experimental Proofs of A Drug’s DNA Specificity....Pages 579-603
