Introduction to Bioorganic Chemistry and Chemical Biology

504 Pages·2012·30.84 MB·English

by  David Van Vranken

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Chemical Biology
ISBN 0-8153-4076-1
David Van Vranken
9 780815 340768 www.garlandscience.com and Gregory Weiss
Introduction to Bioorganic Chemistry
and Chemical Biology
David Van Vranken and Gregory Weiss

Introduction to Bioorganic Chemistry
and Chemical Biology
David Van Vranken and Gregory Weiss
Garland Science David Van Vranken earned his PhD in chemistry from Stanford
Vice President: Denise Schanck University. He is a professor of chemistry at UC Irvine, where he
Editor: Summers Scholl carries out research on chemical structure and reactivity in peptides,
Senior Editorial Assistant: Kelly O’Connor bioactive natural products, and transition metal catalyzed reactions.
Illustrator, Cover, and Text Design: Matthew McClements,
Blink Studio, Ltd. Gregory Weiss earned his PhD in chemical biology from Harvard
Production Editor and Layout: EJ Publishing Services University. He is a professor of chemistry, molecular biology, and
Development Editor: John Murdzek biochemistry at UC Irvine, where his laboratory focuses on the
Copyeditor: Bruce Goatly interface between chemistry and biology, including combinatorial
Proofreader: Jo Clayton chemistry applied to antiviral drug discovery, membrane proteins,
Indexer: Bill Johncocks and bioelectronics.
© 2013 by Garland Science, Taylor & Francis Group, LLC
This book contains information obtained from authentic and highly
regarded sources. Every effort has been made to trace copyright holders
and to obtain their permission for the use of copyright material. Reprinted
material is quoted with permission, and sources are indicated. A wide
variety of references are listed. Reasonable efforts have been made to
publish reliable data and information, but the author and the publisher
cannot assume responsibility for the validity of all materials or for the
consequences of their use. All rights reserved. No part of this publication
may be reproduced, stored in a retrieval system or transmitted in any
form or by any means—graphic, electronic, or mechanical, including
photocopying, recording, taping, or information storage and retrieval
systems—without permission of the copyright holder.
ISBN 978-0-8153-4214-4
Library of Congress Cataloging-in-Publication Data
Van Vranken, David L.
Introduction to bioorganic chemistry and chemical biology / David L.
Van Vranken, Gregory A. Weiss.
p. cm.
Includes bibliographical references and index.
ISBN 978-0-8153-4214-4 (pbk.)
1. Biochemistry. I. Weiss, Gregory A. II. Title.
QD415.V36 2013
572--dc23
2012019693
Published by Garland Science, Taylor & Francis Group, LLC,
an informa business, 711 Third Avenue, New York, NY 10017,
USA, and 3 Park Square, Milton Park, Abingdon, OX14 4RN, UK.
Printed in the United States of America
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Visit our website at http://www.garlandscience.com
v
Preface
This textbook provides a chemical blueprint with which to understand the synthesis
and function of molecules that comprise living cells. In order to tackle chemical
biology—a field of vast breadth and depth—as it continues to expand and evolve, we
focus on the organic chemistry of biooligomers. Biooligomers are responsible for every
main function of the cell, including control, communications, and manufacturing.
The central dogma of molecular biology serves as an organizing principle for students
embarking on a tour of these molecules. Starting at the level of genes and advancing
through each class of biooligomer—DNA, RNA, proteins, glycans, polyketides, and
terpenes—we study their chemistry, structure, and interactions with other molecules.
Ultimately, we return to the topic of chemical control over gene expression. Although
the majority of studies during the past millennium were based on model organisms,
we concentrate on human cells as much as possible.
Introduction to Bioorganic Chemistry and Chemical Biology is written for upper-
division undergraduate students and graduate-level students who have completed a
year of organic chemistry. No initial knowledge of biology is assumed, but some famil-
iarity is beneficial. The book is also appropriate for advanced students in the health
sciences. A series of chemical biology courses we teach at the University of California,
Irvine, inspired the development of this book. Every student in our courses speaks a
common language—organic chemistry—but there was no single textbook to provide
an adequate description of the cell at the level of atoms, bonds, and arrow-pushing
reaction mechanisms. Starting with foundational and simple concepts, the book
gradually builds in complexity, across sections and chapters. For the undergraduate
course, we simply skip the more advanced topics in both the reading assignments
and lectures. This format offers flexibility in coverage, depending on the length of the
course and the level of student.
This book is organized according to the central dogma of molecular biology.
Chapters 1 and 2 cover the fundamentals of chemical biology and the chemical origins
of biology, respectively. Each subsequent chapter (3–8) focuses largely on one type of
biooligomer in a human cell: DNA, RNA, proteins, glycans, polyketides, and terpe-
nes. We steer clear of the metabolic and biosynthetic pathways, which have become
synonymous with introductory biochemistry courses. Chapter 9 catapults the student
beyond the central dogma to explain mechanisms of cellular control over the produc-
tion of biooligomers. This final chapter will bring students closest to an understand-
ing of modern biology, physiology, and medicine. We recognize the relentless pace
of new technology to emerge and quickly become antiquated; therefore, we limit our
discussion of instrumentation and laboratory techniques. Since Introduction to Bioor-
ganic Chemistry and Chemical Biology is not intended to be comprehensive, many
well-known examples and techniques from the field of chemical biology are omit-
ted. Furthermore, we fully expect that instructors will select from and supplement the
material in the book with additional information that best meets the needs of their
students.
vi PReFAce
From experience, we know that composing moving, informative lectures consti-
tutes the fun part of teaching. In this vein, each chapter begins with a snapshot of
a significant discovery by luminaries such as Dorothy Crowfoot Hodgkins, Phoebus
Levene, and Hermann Emil Fischer. We tell the stories of early examples of chemical
biology illustrated in the Iliad and ancient Egyptian pharmacopeias. Our book com-
bines rich, full color imagery with relevant biological examples to engage the reader
as the combinatorial molecular architecture of life is revealed. Our choice of colors is
deliberate: in general, we use red for DNA, green for RNA, blue for proteins, purple
for glycans, and brown for polyketides and terpenes. Therefore, when biooligomers
are represented by abstract shapes, the color of the shape offers an additional level
of biochemical information. We employ modern depictions of organic structures and
mechanistic arrow-pushing in a way that will be familiar to all students who have taken
an introductory course in organic chemistry. Biological macromolecules are rendered
to reveal their secondary structures and PDB codes are included to allow students to
interact directly using the Protein Data Bank website. In-text problems are situated
throughout the chapters, contextualized for greater understanding; additional prob-
lems are found at the end of each chapter. We have starred (*) those problems best
suited to self-study, and solutions are available online at the Student Resource Site.
Chapters also begin with a list of general Learning Objectives and end with a list of
specific Learning Outcomes to focus students on important topics of comprehension.
David L. Van Vranken and Gregory A. Weiss
Online ResOuRces
Accessible from www.garlandscience.com/bioorganic-chembio, the Student and
Instructor Resource Websites provide learning and teaching tools created for Intro-
duction to Bioorganic Chemistry and Chemical Biology. The Student Resource Site is
open to everyone, and users have the option to register in order to use book-marking
and note-taking tools. The Instructor Resource Site requires registration and access
is available to instructors who have assigned the book to their course. To access
the Instructor Resource Site, please contact your local sales representative or email
[email protected]. Below is an overview of the resources available for this book.
On the Website, the resources may be browsed by individual chapters and there is a
search engine. You can also access the resources available for other Garland Science
titles.
For students
Flashcards
Each chapter contains a set of flashcards that allow students to review key terms from
the text.
Glossary
The complete glossary from the book and can be searched and browsed as a whole or
sorted by chapter.
References
For each chapter, a list of references is organized by concept headings.
Problems
Solutions to all in-text problems as well as all starred (*) end-of-chapter problems are
available to students. 
For instructors
Figures
The images from the book are available in two convenient formats: PowerPoint® and
JPEG. They have been optimized for display on a computer. Figures are searchable by
figure number, figure name, or by keywords used in the figure legend from the book.
Solutions
Solutions to all problems (in-text and end-of-chapter) are available to qualified adop-
ters.
vii
Acknowledgments
First and foremost, without the unwavering love and support of our families, this
book wouldn’t have become a reality. Our love and deep appreciation are given to
Maureen, Julia, and Kim.
This book also owes a debt of gratitude to a cast of thousands—the researchers in
the field who did the work we have had the privilege of describing. It’s impossible to
single out every one of these deserving scientists for acknowledgement. Limitations
of space in this introductory text imposed agonizing brevity. We omitted important
contributions made by key players, and we mentioned seminal discoveries without
attribution. We greatly appreciate the efforts of those who drove the field forward.
We thank the following authors for writing textbooks we found particularly inspi-
rational: Bruce Alberts, Ian Fleming, Clayton Heathcock, Alexander Johnson, Jack
Kyte, Julian Lewis, Martin Raff, Keith Roberts, Richard Silverman, Wolfram Saenger,
Andrew Streitwieser, Christopher Walsh, and Peter Walter. We also appreciate the
countless students at UC Irvine who patiently endured our test drives of the material
during our teaching. We are also grateful for the friendship and support of our col-
leagues at UC Irvine.
The Garland Science team made this challenging project manageable. We would
like to thank our editor, Summers Scholl, who managed this project with panache; tal-
ented developmental editor John Murdzek; the unflappable senior editorial assistant
Kelly O’Connor who kept the project on track and watched over a million details; and
production editor Emma Jeffcock for expert layout and other crucial matters. Addi-
tionally, the illustrations benefited from the wonderful artistry of Matt McClements;
and Becky Hainz-Baxter sifted through thousands of possibilities to find perfect pho-
tos and permissions.
The following people provided valuable commentary as readers, reviewers, and
advisors during the development of the project:
Peter A. Beal (University of California, Davis); Annette Beck-Sickinger (University of
Leipzig); Danielle Dube (Bowdoin College); Marina Gobbo (University of Padova);
David Grayson (Trinity College, Dublin); Paul Harrison (McMaster University); Jessica
Hollenbeck (Trinity University, Texas); Gerwald Jogl (Brown University); Andrej Lup-
ták (University of California, Irvine); José Luis Mascareñas (University of Santiago);
Christian Melander (North Carolina State University); Nicola Pohl (Indiana State Uni-
versity); James Redman (Cardiff University); Carmelo J. Rizzo (Vanderbilt University);
Erland P. Stevens (Davidson College); Terry Smith (University of St. Andrews); Ali
Tavassoli (University of Southampton); Doug Tobias (University of California, Irvine).
viii
Dedication
This book is dedicated to our graduate mentors, Pete and Stuart.
ix
Contents
chapter 1 The Fundamentals of chemical Biology 1
chapter 2 The chemical Origins of Biology 27
chapter 3 DnA 57
chapter 4 RnA 131
chapter 5 Peptide and Protein structure 179
chapter 6 Protein Function 229
chapter 7 Glycobiology 281
chapter 8 Polyketides and Terpenes 339
chapter 9 chemical control of signal Transduction 397
Glossary 461
index 469