HOST-GUEST MOLECULAR INTERACTIONS. FROM CHEMISTRi TO BIOLOGY The Ciba Foundation is an international scientific and educational charity. It was established in 1947 by the Swiss chemical and pharmaceutical company of ClBA Limited- now CIBA-GEIGY Limited. The Foundation operates independently in London under English trust law. The Ciba Foundation exists to promote international cooperation in biological, medical and chemical research. It organizes about eight international multidisciplinary symposia each year on topics that seem ready for discussion by a small group of research workers. The papers and discussions are published in the Ciba Foundation symposium series. The Foundation also holds many shorter meetings (not published), organized by the Foundation itself or by outside scientific organizations. The staff always welcome suggestions for future meetings. The Foundation’s house at 41 Portland Place, London W1N 4BN, provides facilities for meetings of all kinds’. Its Media Resource Service supplies information to journalists on all scientific and technological topics. The library, open five days a week to any graduate in science or medicine, also provides information on scientific meetings throughout the world and answers general enquiries on biomedical and chemical subjects. Scientists from any part of the world may stay in the house during working visits to London. Ciba Foundation Symposium 158 - - ____ ~ ~ HOST-GUEST MOLECULAR INTERACTIONS: FROM CHEMISTRY TO BIOLOGY A Wiley-lnterscience Publication 1991 JOHN WILEY & SONS _ _ ~~ Chichester . New York . Brisbane Toronto . Singapore OCiba Foundation 1991 Published in 1991 by John Wiley & Sons Ltd. Baffins Lane, Chichester West Sussex PO19 IUD, Ergland All rights reserved. No part of this book may be reproduced by any means, or transmitted, or translated into a machine language without the written permission of the publisher. Other Wiley Editorial Offic<?s John Wiley & Sons, Inc., 6135 Third Avenue, New York, NY 10158-0012, USA Jacaranda Wiley Ltd, G.P.O. Box 859, Brisbane, Qucensland 4001, Australia John Wiley & Sons (Canada) Ltd, 22 Worcester Road, Rexdale, Ontario M9W Canada 1L1, lohn Wiley & Sons (SEA) Pte Ltd, 37 Jalan Pemirnpin 05-04, Block B, Union Industrial Huilding, Singapore 2057 Suggested series entry for library catalogues: C'iba Foundation Symposia Ciba Foundation Symposiuin 158 ix+278 pages, 80 figures, 21 tables, 15 structures 1,ibrarv of Congress Cataloging-in-Publication Data Host-guest molecular interiictions: l'rom chemistry to biology. p. cm.-(Ciba Foundation symposium; 158) Proceedings of the Symposium on Host-Guest Molecular Interactions: from Chemistry to Biology held at the Ciba Foundation, London, Jul. 3-5, 1990. Includes 'bibliographical references and index. ISBN 0-471-92958-1 I, Ligand binding (Biochemistry)-Congresses. 2. Drugs-Design- Congresea. 3. Protein engineering-Congresses. 4. Protein binding-Congresses. I. Symposium on Host-Guest Molecular Interactions: from Chem:,stry to Biology (1990: Ciba Foundation) I I. Series. QP517.L54H67 1990 574.19 ' 245-dc20 91-330 CIP British Library Cafalogrrinp in Publication Data Host-guest molecular interactions: from chemistry to biology.-(CIBA Foundation Symposia) I. Sutherland, I. 0. 11. Series 541.2 ISBN 0 471 92958 I Phototypeset by Dobbie Typesettinl: Limited, Tavistock, Devon. Printed and bound in Great Britain by Biddles Ltd., Guildford. Contents Symposium on Host-Guest Molecular Interactions: from Chemistry to Biology, held at the Ciba Foundation, London 3-5 July 1990 Editors: Derek J. Chadwick (Organizer) and Kate Widdows 1. 0. Sutherland Introduction 1 J. F. Stoddart Molecular self-assembly processes 5 Discussion 17 G. W. Gokel Self-assembly in supramolecular systems 23 Discussion 3 1 General discussion I Flexibility or rigidity? 39 D. N. Reinhoudt, W. F. Nijenhuis and P. D. van der Wal Host-guest interactions in thin membranes: selective ion transport and transduction into electronic signals 42 Discussion 5 1 W. J. Albery Molecular recognition and molecular sensors 55 Discussion 67 J. P. Waltho and D. H. Williams The natural design of vancomycin family antibiotics to bind to their target peptides 73 Discussion 87 General discussion I1 Crystals as supramolecules 92 Molecular devices and sensors 95 J. Rebek Clefts as receptor and enzyme analogues 98 Discussion 109 R. Breslow Enzyme mimics 115 Discussion 122 V vi Contents M. J. Waring Binding of antibiotics to DNA 128 Discussion 142 T. Montenay-Garestier*, C. HClCne and N. T. Thuong Design of sequence-specific bi runctional nucleic acid ligands 147 M. H. Caruthers, G. Beaton, L. Cummins, D. Graff, Y.-X. Ma, W. S. Marshall, H. Sasmor, P. Norris and E. K. Yau Synthesis and biochemical studies of dithioate DNA 158 Discussion 166 G. C. K. Roberts Conformational flexibility and protein specificity 169 Discussion 182 R. I. Carey, K.-H. Altmann and M. Mutter Protein design: template- assembled synthetic proteins 187 Discussion 199 General discussion I11 Transition state theory and energy requirements for reaction 204 A. B. Edmundson, D. L. Harris, G. Tribbick and H. M. Geysen Binding of peptides to proteins: an exercise in molecular design 213 Discussion 225 R. U. Lemieux, L. T. J. Delbaere, H. Beierbeck and U. Spohr Involvement of water in host-guest interactions 23 I Discussion 245 J. G. Vinter and M. It. Sauriders Molecular modelling approaches to host-guest complexes 249 Discussion 262 1. 0. Sutherland Summing-up 266 Index of contributors 269 Subject index 271 *Dr Montenay-Carestier was unable to attend the symposium. Her paper was presented by Dr Michael Waring. Participants W. J. Albery University College, Oxford OX1 4BH, UK C. I. BrandCn Swedish University of Agricultural Sciences, Department of Molecular Biology, Uppsala Biomedical Center, PO Box 590, S-751 24 Uppsala, Sweden E. Breslow Department of Biochemistry, The New York Hospital-Cornell Medical Center, 1300 York Avenue, New York, NY 10021, USA R. Breslow Department of Chemistry, Columbia University, New York, NY 10027, USA R. I. Carey Institut de Chimie Organique, UniversitC de Lausanne, Rue de la Barre 2, CH-1005 Lausanne, Switzerland M. H. Caruthers Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309-0215, USA A. Collet StCrCochimie et Interactions MolCculaires, Ecole Normale Superieure de Lyon, 46 AllCe d’Italie, F-69364 Lyon cedex 7, France M. J. Crumpton Imperial Cancer Research Fund Laboratories, PO Box 123, Lincoln’s Inn Fields, London WC2A 3PX, UK J. D. Dunitz Laboratorium fur Organische Chemie, ETH-Zentrum, Universitatstrasse 16, CH-8092 Zurich, Switzerland A. B. Edmundson Harrington Cancer Center, 1500 Wallace Boulevard, Amarillo, TX 79106, USA G. W. Gokel Department of Chemistry, University of Miami, Coral Gables, FL 33124, USA C. D. Gutsche Department of Chemistry, Texas Christian University, Fort Worth, TX 76129, USA vii Vlll Participants A. D. Hamilton Department of Chemistry, University of Pittsburgh, Pittsburgh, PA 15260, USA R. M. Kellogg Department of Organic Chemistry, University of Groningen, Nijenborgh 16, Groningen 9747 AG, The Netherlands 0. Kennard University Chemical Laboratories, University of Cambridge, Lensfield Road, Cambridge CB2 lEW, UK R. U. Lemieux Department of Chemistry, Faculty of Science, University of Alberta, E5-52 Chemistry Building East, Edmonton, Alberta, Canada, T6G 2G2 W. Miiller Institute of Organic Chemistry, University of Mainz, J J Becher Weg 18-22, 11-6500 Mainz 1, Federal Republic of Germany D. Parker Department of Chemistry, Science Laboratories, University of Durham, South Roa.d, Durham DHl 3LE, UK J. Rebek Departmenl, of Chemistry, Massachusetts Institute of Technology, Building 18-207, 77 Massachusetts Avenue, Cambridge, MA 02139, USA D. N. Reinhoudt Laboratory of Organic Chemistry, Twente University, PO Box 217, NL-7500 AE Enschede, The Netherlands G. C. K. Roberts Department of Biochemistry, University of Leicester, Adrian Building, University Road, Leicester LEI 7RH, UK C. Sacht (Ciba Founddion Bursar) Department of Chemistry, University of Cape Town, Private Bag, Rondebosch 7700, Cape Province, South Africa J. Stoddart Department of Chemistry, University of Sheffield, F. Sheffield S3 7HF and The School of Chemistry, University of Birmingham, Edgbaston, Birmingham B 15 2TT, UK I. 0. Sutherland (Chairman) Department of Chemistry, University of Liverpool, PO Box 147, Liverpool L69 3BX, UK J. G. Vinter Molecular Recognition Unit, University Chemical Laboratories, University of Cambridge, Lensfield Road, Cambridge CB2 1EW and Department of Chemistry, University College London, 20 Gordon Street, London WClH OAJ, UK Participants IX J. P. Waltho Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield S10 2TN, UK M. J. Waring Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 lQJ, UK Novartis Foundation Symposium Edited by Derek J. Chadwick, Kate Widdows Copyright 0 1991 by Ciba Foundation lntroduc tion Ian Sutherland Department of Chemistry, University of Liverpool, PO Box 147, Liverpool L69 3BX, UK This meeting is ambitious in its breadth; it ranges from biology to chemistry, but I suspect the actual scope of the meeting will be defined by the papers and the interests of the participants. Otherwise, it would be impossibly broad. The origins of the meeting date back to my postgraduate days in the 1950s, when, unknown to me, many of the foundations of molecular biology were being laid down in nearby laboratories. At that time, the crystal structures of proteins were being examined and the double helix of DNA was discovered. Molecular biology really took off from there and has grown explosively ever since. A number of molecular biologists are here to represent the biological end of the spectrum. I believe that the basic principles are chemical and that there is complete overlap of biology and chemistry, but I have to recognize that different people emphasize different aspects of our topic. In the 1950s, again unknown to me, work on clathrates was proceeding in Oxford. H.M. Powell began the work on clathrates and host-guest chemistry in the solid state, and this is now an active and expanding area. At this meeting we are not going to talk much about clathrates, but we will talk a great deal about complexes in solution. Also in the 1950s, Fritz Cramer was working on cyclodextrins. Cyclodextrin chemistry was the first example of host-guest chemistry using relatively small host molecules, but this work did not attract as much attention at the time as it deserved. Organic chemists became interested in the field of host-guest chemistry after the discovery of crown ethers in 1967. The impact crown ethers had was quite considerable, but the ripple created then has since grown enormously. Crown ethers have sparked off a great deal of synthetic effort and imagination in the chemical community; new compounds and families of compounds have appeared, many of which will feature in this meeting. It certainly seemed appropriate to bring these areas together in a single meeting. Intermolecular interactions and molecular assemblies will play an extremely important role in chemistry in the future. For biologists, of course, they have always been the most important thing-all biology is based on molecular assemblies-but they are now coming into the orbit of the synthetic chemist. We shall hear about methods for making organized assemblies of synthetic molecules, which may have specific purposes. New materials and molecular electronics are certainly going to require synthetic molecular assemblies 1