E-Book Overview
Due to their high specificity and low toxicity profile, peptides have once again become central to the development of new drugs. In <EM>Peptide-Based Drug Design: Methods and Protocols, expert researchers provide a handbook which offers a selection of research and production tools suitable for transforming a promising protein fragment or stand-alone native peptide into a pharmaceutically acceptable composition. The volume delves into contemporary, cutting-edge subjects such as hit isolation and target validation, computer-aided design, sequence modifications to satisfy pharmacologists, in vivo stability and imaging, and the actual production of difficult sequences. Written in the highly successful <EM>Methods in Molecular Biology™ series format, chapters include readily reproducible, step-by-step laboratory protocols, lists of materials, and the Notes section, which highlights tips on troubleshooting and avoiding known pitfalls.
Comprehensive and up-to-date, <EM>Peptide-Based Drug Design: Methods and Protocols shows its subject to be an independent science on the rise, and provides scientists with a clear, concise guide for continuing this vital research.
E-Book Content
Peptide-Based Drug Design
M E T H O D S I N M O L E C U L A R B I O L O G YTM
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M E T H O D S I N M O L E C U L A R B I O L O G YT M
Peptide-Based Drug Design
Edited by
Laszlo Otvos
Editor Laszlo Otvos, PhD Center for Biotechnology Temple University Philadelphia, PA 19122
Series Editor John M. Walker School of Life Sciences University of Hertfordshire Hatfield, Hertfordshire Al10 9 AB UK
ISBN: 978-1-58829-990-1 DOI: 10.1007/978-1-59745-419-3
e-ISBN: 978-1-59745-419-3
Library of Congress Control Number: 2008930838 C 2008 Humana Press, a part of Springer Science+Business Media, LLC All rights reserved. This work may not be translated or copied in whole or in part without the written permission of the publisher (Humana Press, 999 Riverview Drive, Suite 208, Totowa, NJ 07512 USA), except for brief excerpts in connection with reviews or scholarly analysis. Use in connection with any form of information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed is forbidden. The use in this publication of trade names, trademarks, service marks, and similar terms, even if they are not identified as such, is not to be taken as an expression of opinion as to whether or not they are subject to proprietary rights.
Printed on acid-free paper 987654321 springer.com
Preface Natural products chemistry books usually open with a chapter on amino acids, peptides, and proteins. Peptides represent the interaction site between bioactive proteins. Together with peptide hormones, these molecules promise to be the starting points of drug development. Indeed, with the fast advances of peptide synthetic techniques, injectable peptide drugs obtained regulartory approval. Currently, peptide/protein drugs contstitute more than 10% of the ethical drug market. However, they are orally not available and expensive to mass produce. Thus, in the late 1980s, pharmaceutical companies quickly abandoned peptide research and focused on small molecules with more advantageous in vivo stability and pharmacokinetic properties. At the turn of the new century, the unexpected toxicity and cross-reactivity of small molecule drugs turned investors back to peptides, with their high specificity and, in most cases, low toxicity profile. The 15 years in exile was not completely useless; we all learned how to modify peptides to be competitive with small molecules in the drug development