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The past decade has witnessed a burst of activity and interest in the discovery and design of drugs that cleave DNA and RNA with sequence specificity. This interest stems from the potential of this class of compounds to be useful as therapeutics agents, in particular in the field of the treatment of cancer and viral diseases. Further, a side benefit of such studies is the discovery of novel mechanisms and uses of such agents as tools in the study of structure and function of nucleic acids. Up to now, no international meeting has been organized to recognize the immense progress that has been made in this field. The field of DNA and RNA cleavage by natural and chemical drugs now includes researchers working with rather dissimilar agents but with common underlying mechanisms of DNA damage. Until recently, these scientists were working in separate, apparently unrelated areas, such as the enediyne antibiotics and their synthetic analogues, bleomycin-metal complexes, metal-drug complexes, ribozymes and ribozyme mimics, and antisense and antigene oligonucleotides, etc. It is now clear that these research areas have in common strategies and targets. Researchers representing these areas worked together at this workshop where these common interests were discussed and scientific ideas modified and criticized. Such a workshop should lead to new research approaches and collaborative interactions, and is expected to significantly enhance the progress in the field of DNA and RNA cleavage.
List of contents
Preface xi.- List of Contributors xiii.- List of Participants xvii.- DNA cleavage by enediyne molecules.- Enediynes as Probes of Nucleic Acid Structure.- The Intrinsic Flexibility and Drug-Induced Bending of Calicheamicin DNA Targets.- Recent Biophysical and Biological Studies on the Mechanism of Action of Calicheamicin.- Kedarcidin and Maduropeptin, Two Novel Chromoproteins with Potent Antitumor Activities.- Dynemicin A, a Novel Enediyne DNA Cutter.- Bleomycin: the paradigm of DNA cleavers based on metal complexes.- Polynucleotide Cleavage and the Expression of Antitumor Activity by Bleomycin.- Bleomycin Reaction Pathways: Kinetic Approaches.- Selected Generation and Cleavage of C4'-Modified Oligonucleotides.- Site-specific DNA cleavage.- Site Specific Oxidative Scission of Nucleic Acids and Proteins.- Sequence Selective DNA Cleavage by PNA-NTA Conjugates.- The Synthesis and DNA/RNA Hybridization Properties of DNG, a Putative Antisense Agent with an Attractive Polycationic Guanidinium Backbone.- Design of Photoactivatable DNA-Cleaving Amino Acids with High Sequence Selectivity.- Rational Design of a New Class of DNA Cleaver Based on Prediction of Minor Groove Binding Interactions and NMR Structural Studies.- Binary Systems of Oligonucleotide Conjugates for Sequence Specific Energy-Transfer Sensitized Photomodification of Nucleic Acids.- Mechanism of oxidative DNA cleavage.- Targeted Oxidative DNA Cleavage Mediated by Oligonucleotide-Cationic Metalloporphyrin Conjugates.- Pulse Radiolysis and Laser Photolysis Studies on Nucleotide Radicals. The Protonation State of the Radicals.- Redox Regulation of the Human Immunodeficiency Virus Type 1 (HIV-1).- RNA cleavage by RNase H.- Ribonuclease H: from Enzymes to Antisense Effects of Oligonucleotides.- Hydrolysis of RNA byribozymes and metal complexes.- Structure, Activity and Application of Chemically Modified Hammerhead Ribozymes.- The Hairpin Ribozyme.- Sequence-Specific Cleavage of RNA Using Lanthanide Complexes Linked to Oligonucleotides.- Synergism of Two Metal Ions for the Hydrolysis of DNA and RNA.- Texaphyrin-Based Nuclease Analogues. Rationally Designed Approaches to the Catalytic Cleavage of RNA and DNA Targets.- Ribozyme Mimics for Catalytic Antisense Strategies.
