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DNA sequence specificity is a sub-specialty in the general area of molecular recognition. This area includes macromolecular-molecular interactions (e.g., protein-DNA), oligomer-DNA interacitons (e.g., triple strands), and ligand-DNA interactions (e.g., drug-DNA). It is this latter group of DNA sequence specificity interactions that is the subject of Volumes 1 and 2 of Advances in DNA Sequence Specific Agents. As was the case for Volume 1, Part A also covers methodology, but in Volume 2 we include calorimetric titrations, molecular modeling, X-ray crystallographic and NMR structural studies, and transcriptional assays. Part B also follows the same format as Volume 1 and describes the sequence specificities and covalent and noncovalent interactions of small ligands with DNA.This volume is aimed in general at scientists who have an interest in deciphering the molecular mechanisms for sequence recognition of DNA. The methods have general applicability to small molecules as well as oligomers and proteins, while the examples provide general principles involved in sequence recognition.

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ADVANCES IN DNA SEQUENCE SPECIFIC AGENTS Volume2 9 1996 This Page Intentionally Left Blank ADVANCES IN DNA SEQUENCE SPECIFIC AGENTS Series Editor: LAURENCE H. HURLEY The Drug Dynamics Institute The University of Texas at Austin Volume Editor: JONATHAN B. CHAIRES Department of Biochemistry University of Mississippi Medical Center Jackson, Mississippi VOLUME2 * 1996 @ Greenwich, Connecticut JA! PRESS INC. London, England Copyright 91996 by JAI PRESS INC. 55 Old Post Road, No. 2 Greenwich, Connecticut 06836 JAI PRESS LTD. The Courtyard 28 High Street Hampton Hill, Middlesex TWl 2 1PD England All rights reserved. No part of this publication may be reproduced, stored on a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, filming, recording, or otherwise, without prior permission in writing from the publisher. ISBN: 1-55938-166-3 Manufactured in the United States of America CONTENTS LIST OF CONTRIBUTORS PREFACE Laurence H. Hurley and Jonathan B. Chaires vii ix PART !. METHODS USED TO EVALUATE THE MOLECULAR BASIS FOR SEQUENCE SPECIFICITY CALORIMETRIC STUDIES OF DRUG-DNA INTERACTIONS Luis A. Marky, Karen Alessi, and Dionisios Rentzeperis MOLECULAR MODELING OF DRUG-DNA INTERACTIONS" FACTS AND FANTASIES John O. Trent and Stephen Neidle X-RAY CRYSTALLOGRAPHIC AND NMR STRUCTURAL STUDIES OF ANTHRACYCLINE ANTICANCER DRUGS: IMPLICATION IN DRUG DESIGN Andrew H.-J. Wang TRANSCRIPTIONAL ASSAY FOR PROBING MOLECULAR ASPECTS OF DRUG-DNA INTERACTIONS Don R. Phillips 29 59 101 PART II. SEQUENCE SPECIFICITY OF DNA INTERACTIVE DRUGS MOLECULAR RECOGNITION OF DNA BY DAUNORUBICIN Jonathan B. Chaires 141 CONTENTS COVALENT INTERACTIONS OF ETHIDIUM AND ACTINOMYCIN D WiTH NUCLEIC ACIDS: PHOTOAFFINITY LABELING OF DNA David E. Graves 169 DNA BINDING OF DINUCLEAR PLATINUM COMPLEXES Nicholas Farrell 187 DNA SEQUENCE SELECTIVITY OF THE PYRROLE-DERIVED, BIFUNCTIONAL ALKYLATING AGENTS Paul B. Hopkins INDEX 217 241 LIST OF CONTRIBUTORS Karen Alessi Department of Chemistry New York University New York, New York Jonathan B. Chaires Department of Biochemistry University of Mississippi Medical Center Jackson, Mississippi Nicholas Farrell Department of Chemistry Virginia Commonwealth University Richmond, Virginia David E. Graves University of Mississippi University, Mi
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