Bleomycin: Chemical, Biochemical, and Biological Aspects: Proceedings of a Joint U.S.-Japan Symposium Held at the East-West Center, Honolulu, July 18-

ISBN-13: 9781461261933 / Angielski / Miękka / 2011 / 351 str.

Sidney M. Hecht; Sidney M. Hecht

Opis

This book records the proceedings of a joint U.S.-Japan symposium on the chem istry, biochemistry, and biology of bleomycin, an antitumor antibiotic shown to be effective therapeutically against, eg, squamous cell carcinomas, Hodgkin's lymphoma, and testicular tumors. Several important and previously unreported observations were presented and the status of experimental work in the United States and Japan was reviewed; a summary and interpretation of the scientific presentations at the meeting has been prepared by the editor and is included as the first contribution in this volume. In addition to the symposium contributions, an experimental section has been included at the end of the book dealing with practical methods for the fractiona tion, modification, and assay of bleomycin. It is hoped that this section will facilitate progress in this area of scientific endeavor. The symposium from which this book is derived was organized by Drs. Umezawa, Takita, and Hecht and supported financially by the National Science Foundation, the National Cancer Institute, and the Japan Society for the Promotion of Science. S. M. Hecht v Contents Status Reports Summary of the Bleomycin Symposium. S. M. HECHT .............. 1 Advances in Bleomycin Studies. H. UMEZAWA ..................., 24 Review of the Structural Studies on Bleomycin. T. TAKITA . . . . . . . .. . . 37 . Synthetic and Biosynthetic Studies Studies on the Total Synthesis of Bleomycin. S. M. HECHT, D. 1. BURLETT, Y. MUSHIKA, Y. KURODA, and M. D. LEVIN .......... 48 A Synthetic Approach to the Pyrimidine Moiety of Bleomycin.

Spis treści

Contentst.- Status Reports.- Summary of the Bleomycin Symposium.- Advances in Bleomycin Studies.- Review of the Structural Studies on Bleomycin.- Synthetic and Biosynthetic Studies.- Studies on the Total Synthesis of Bleomycin.- A Synthetic Approach to the Pyrimidine Moiety of Bleomycin.- Biogenetic Aspects of Bleomycin-Phleomycin Group Antibiotics.- Physical and Spectral Analysis of Bleomycin.- Liquid Chromatography of Bleomycin.- NMR Study of Bleomycin.- Bleomycin as a Metal Chelator.- 1H-NMR Study of the Metal Binding Sites of Bleomycin.- The Metallobleomycins.- Metal Complex of Bleomycinand Its Implication for the Mechanism of Bleomycin Action.- Electron Spin Resonance Studies of 1: 1:1 Bleomycin-Cobalt(II)-Oxygen Adduct Complex.- Interaction of Bleomycin with DNA.- A Role for Iron in the Degradation of DNA.- Contribution of the Superoxide Anion-Hydroxyl Radical Pathway to the Cleavage of DNAby Bleomycin.- Interaction of Bleomycinwith DNA.- A Molecular Basis for the Interaction of Bleomycin with DNA.- Molecular Aspects of Bleomycin-Promoted Damage of Covalently Closed Circular DNA.- The Use of Covalently Closed Circular DNA to Investigate Properties of Bleomycin and Its Analogs.- The Action of Bleomycin on DNA.- Biological Effects of Bleomycin.- Polyamines and the Toxicity of the Bleomycins.- Cytotoxicity of the Various Bleomycins to Cultured Mammalian Cells.- Upward-Concave Dose-Response Relationship in Bleomycin Lethality of Mammalian Cells.- Conjugation of Bifunctional Chelating Agents to Bleomycin for Use in Nuclear Medicine.- Bleomycin-Induced Pulmonary Toxicity: A Model for the Study of Pulmonary Fibrosis.- Concluding Remarks at the Symposium on Bleomycin.- Practical Methods for the Manipulation and Assay of Bleomycin.- A Practical Method for the Separation of Bleomycin Components.- Preparation of Bleomycinic Acid from Bleomycin A2.- A Practical Method for Preparing Copper-Free Bleomycin A2.- A Simple Assay for Bleomycin Activity: Degradation of Radioactive DNA to Acid-Soluble Products.