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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
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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