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Peptidomimetics have found wide application as bioavailable, and often potent mimetics of natural peptides. They form the basis of important classes of enzyme inhibitors, they act as receptor agonists and antagonists, and they have even been used to mimic DNA structure. Recent advances in the use of solid-phase organic synthesis have paved the way for the preparation of libraries of these structures to allow the rapid optimization of theri biological properties and hence therapeutic potential. We are also beginning to gain a greater understanding of the structural features of this class of compounds that influence their ability to permeate membranes, and their rate of clearance and metabolism. This volume brings together many of these critical issues by highlighting recent advances in a number of core peptidomimetic-based research.
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ADVANCES IN AMINO ACID MIMETICS AND PEPTlDOMIMETICS This Page Intentionally Left Blank ADVANCES IN AMINO ACID MIMETICS AND PEPTIDOMIMETICS Editor: ANDREW ABELL Department of Chemistry University of Canterbury Christchurch, New Zealand VOLUME2 9 1999 JAI PRESS INC. Stamford, Connecticut Copyright 91999 by JA/ PRESSINC. 1O0 Prospect Street Stamford, Connecticut 06904-0811 All rights reserved. No part of thb 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: 0-7623-0614.9 Transferred to digital printing 2006 CONTENTS LIST OF CONTRIBUTORS PREFACE Andrew Abell ~176 Vll xi COMBINATORIAL SYNTHESIS OF PEPTIDOMIMETICS Owen B. Wallace, Darren L. Whitehouse, and Dharmpal S. Dodd THE DEVELOPMENT OF NOVEL NONCOVALENT THROMBIN INHIBITORS Thomas J. Tucker and Richard C.A. Isaacs PEPTIDOMIMETICS DESIGNED FOR ORAL ABSORPTION Giovanni M. Pauletti RARE PROTEIN TURNS: y-TURN, HELIX-TURN-HELIX, AND cis-PROLINE MIMICS Felicia A. Etzkorn,Jeremy M. Travins, and Scott A. Hart 53 89 125 DESIGN OF NON-PEPTIDE AGONISTS AND ANTAGONISTS FOR NEUROPEPTIDE RECEPTORS David C. Horwell, Martyn C. Pritchard, and Jenny Raphy AMINO ACID MIMETICS AND DESIGN OF PEPTIDOMIMETICS FOR OPIOID AND MELANOCORTIN RECEPTORS:GENERAL PERSPECTIVES Victor J. Hruby and Cheryl A. Slate 165 191 vi CONTENTS PEPTIDE NUCLEIC ACIDS: POTENTIAL AS ANTISENSE AND ANTIGENE DRUGS Anne B. Eldrup and Peter E. Nielsen SOLUTION AND SOLUBLE POLYMER SYNTHESES OF AZATIDES AND AZAPEPTIDES Juyoung Yoon, Hyunsoo Han, and Kim D. Janda 221 247 SUGAR AMINO ACIDS AND CARBOHYDRATES AS SCAFFOLDS AND PEPTIDOMIMETICS Elisabeth Lohof, Fred Burkhart, Markus A. Born, Eckart Planker, and Horst Kessler INDEX 263 293 LIST OF CONTRIBUTORS Markus A. Born Technische Universit~it Mi.inchen Garching, Germany Fred Burkhart Technische Universit~itM0nchen Garching, Germany Dharmpal S. Docld Bristol-Myers Squibb Pharmaceutical Research Institute Princeton, New Jersey Anne B. Eldrup Department of Chemistry University of Copenhagen Copenhagen, Denmark Felicia A. Etzkorn Department of Chemistry University of Virginia Charlottesville, virginia Hyunsoo Han The Department of Chemistry The Scripps Research Institute and The SkaggsInstitute for Chemical Biology La Jolla, California Scott A. Hart Department of Chemistry University of Virginia Charlottesville, Virginia David C. Horwell Parke-Davis Neuroscience