Nucleic Acids (Tutorial Chemistry Texts)

196 Pages·2004·81.89 MB·English

by  Shawn Doonan

Cover images v; Murray Robertsonivisual elements 1998-99, taken froin the
109 Visual Elements Periodic Table, available at www.chemsoc.orgivise1ements
ISBN 0-85404-481-7
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8c
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Preface
The nucleic acids are, in the main, informational macromolecules. DNA
encodes the instructions that are passed on from parents to progeny, so
that the offspring of two human beings is another human being, rather
than any other life form. The related molecule RNA serves the same
function in some viruses, such as the human immunodeficiency virus
(HTV). The nucleic acids are, therefore, responsible for the continuation of
all forms of life on this Earth, and as such are the subject of enormous
interest to biologists.
Why should the student of chemistry be interested in them? The answer
is that the biological roles of the nucleic acids can only be understood in
terms of their chemical structures, and chemists have played a central part
in establishing those structures and the understanding of how they
function. The main objectives of this book are to explain what those
structures are, how they were determined, and how function can be
understood in terms of structure.
Although the nucleic acids are interesting substances in their own right,
the real fascination of their study comes from the interplay between their
chemistry and biology. Indeed, it is not really possible to disentangle the
two, since some of the modern methods for the determination of the
structures of nucleic acids make use of their biological properties. Nucleic
acid chemistry cannot, therefore, be fully understood without some
knowledge of the underlying biology. Consequently, some of the more
important aspects of the fields of molecular biology and genetics are
covered in Chapter 1, and in boxed inaterial throughout the rest of the
book for the benefit of those readers who lack the necessary background
knowledge.
There is also a substantial amount of material in this book about the
history of the subject. Study of the structure and function of nucleic acids
has occupied the attention of a large number of enormously talented
scientists over the last 130 years. This is reflected in the very large number
of Nobel Prizes that have been awarded in the field. A proper
understanding of the present state of our knowledge of the nucleic acids
is, I believe, greatly illuminated by knowing something of how we arrived
at it. It is, by any criterion, a remarkable story of scientific endeavour.
Shawn Doonan
London
iii
TUTORIAL CHEMISTRY TEXTS
rDlTOR IY <HILT CXECUTIVF F.1)I rORS FI)IJCATIONAL COR5IJLIALT
Professor E W AhPl PrqJessor A G DuvieJ Mr M Berry
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Profcjswr J D Woollins
This series of books consists of short, single-topic or modular texts, concentrating on the
rundamental areas of chemistry taught in undergraduate science courses. Each book provides a
concise account of the basiq principles underlying a given subject. embodying an independent-
learning philosophy and including worked examples. Thc one topic, one book approach ensures
that the series is adaptable to chcmistry courses across a variety of institutions.
TITLFS IN THE SERlFS TITLES IN THE SFRIES
Stereochemistry D G Morriy Inorganic Chcniistry in Aqueous Solution
Reactions and Characterization of Solids J Burrr t t
S E Dann
Main Group Chemistry W Henderson
I- 0 KTHCOM I NG TITLFS
d- and f-Block Chemistry C J Jones
Structure and Bonding J Burrett Mechanisms in Organic Reactions
Functional Group Chemistry J R H~nson Organic Spectroscopic Analysis
Orgaiiotransition Metal Chemistry A F Hill
Heterocyclic Chemistry M Suinshurj,
Atomic Structure and Periodicity J Barrrtt
Thermodynamics and Statistical Mechanics
J M Seddon aiid J D Gale
Basic Atomic and Molecular Spectroscopy
J M Hollus
Organic Synthetic Methods J R Hunson
Aromatic Chemistry J D Hepwor,lz.
D R Wuriizg uncl A4 J Wuring
Quantum Mechanics for Chemists
D 0 Hnyivrtrd
Peptides and Proteins S Doonan
Biophysical Chemistry A Cooper
Natural Products: The Secondary
Metabolites J R Humon
Maths for Chemists. Volume I, Numbers,
Functions and Calculus M Corhett und
G Doggett
Maths for Chemists, Volume 11, Power Series,
Complex Numbers and Linear Algebra
A4 C'ockett und G Doggerr
N ucleic Acids
S Doonm
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Contents
1 The Biological Roles of the Nucleic Acids i
1.1 Introduction 1
1.2 Classes of Nucleic Acids 2
1.3 DNA as the Carrier of Genetic Information 4
1.4 An Outline of Protein Structure 12
1.5 Transcription of DNA into RNA 15
1.6 How the Message is Decoded 16
1.7 Protein Synthesis 20
1.8 The “Central Dogma” of Molecular Biology 21
2 The Covalent Structures of Nucleic Acids 25
2.1 The Building Bricks 25
2.2 Nucleosides and Nucleotides 31
2.3 The Inter-nucleotide Linkage 34
2.4 Shorthand Notations 38
2.5 Oligonucleotides 40
2.6 Sizes of Nucleic Acids 41
3 The Three-Dimensional Structure of DNA and
its Implications for Replication 47
3.1 The DNA Double Helix 47
3.2 Why a Double Helix? 62
3.3 The Stability of the Double Helix 65
3.4 Nucleosomes and Chromosomes 67
3.5 DNA Replication 71
3.6 DNA Damage and Repair 77
V
vi Contents
4 Transcription and Translation of
the Genetic Message 85
4.1 The Three-dimensional Structure of RNA 85
4.2 Synthesis of Messenger RNA 87
4.3 Synthesis of Ribosomal and Transfer RNA 97
4.4 Translation of Messenger RNA 98
5 Modern Tools of DNA Analysis 1 9 6
5.1 Introduction: Recent Advances in DNA Technology 116
5.2 Gel Electrophoresis 119
5.3 Restriction Enzymes 123
5.4 Blotting and Hybridization 125
5.5 Making Recombinant DNA Molecules 128
5.6 Cloning 129
5.7 The Polymerase Chain Reaction 135
5.8 DNA Sequencing 138
5.9 Computer Applications in DNA Chemistry 148
5.10 Chemical Synthesis of Oligonucleotides 158
Answers to Problems 171
Subject Index 183
The Biological Roles of
the Nucleic Acids
I. I Introduction
This book is intended mainly for students of chemistry, and so the
emphasis is on the chemistry of the nucleic acids. It is, however, difficult
to talk about the chemistry of these molecules without reference to their
biological properties and functions. Indeed, some of the methods used to
determine the structures of nucleic acids make use of those biological
properties (see Chapter 5). In addition, of course, the biology of the
nucleic acids is a fascinating subject because they are the molecules on
which the continuation of life depends.
Most readers of this book will have studied at least a little biology at
school, and will probably be aware in outline of what DNA is and what it
does. Indeed, living in the modern world it is difficult to avoid hearing
such terms as genes, genomes, genetic engineering and DNA fingerprint-
ing in general usage. Nevertheless, it seems a good idea to start off with a
brief account of what the nucleic acids do, and how they do it, to set the
scene for what comes after. It will be easier to understand the significance
of individual parts of the chemical story if the student has a broad
overview of the biology. Students who are familiar with the topic may
want to skip this chapter and move straight on to the more chemical
material that follows. On the other hand, readers who are interested in
1
2 Nucleic Acids
the biology can find more extensive treatments in the books listed under
Further Reading.
As well as a basic overview, this chapter (and later ones to a lesser
extent) also contains a substantial amount of boxed material which
essentially has to do with the early history of the development of ideas
about genetics and molecular biology. This is partly to correct a common
misapprehension that the study of DNA started in the last couple of
decades of the 20th century. In fact it started in the middle of the 19th
century, and it seems a shame not to be aware of the contributions that
some of the major figures in the field made in those earlier years. In
addition, it might be thought unsatisfactory to accept ideas such as DNA
being the carrier of genetic information without knowing something
about the evidence on which the claim is made. Study of this historical
material is not essential to understanding the bulk of the text, but not to
do so risks failing to appreciate the importance of the contributions made
by earlier generations of scientists working in the field.
1.2 Classes of Nucleic Acids
We need to recognize from the start that there are two classes of nucleic
acids. Both are polymers having a backbone of alternating mono-
saccharide and phosphate units, each of the sugars carrying one of four
possible heterocyclic bases (shown schematically in 1). The main dif-
ference is that in one class the polymer backbone contains 2-deoxyribose,
and the molecule is referred to as deoxyribonucleic acid or DNA. In the
other class the deoxyribose is replaced by ribose, and correspondingly the
molecule is referred to as ribonucleic acid or RNA. We will use these
abbreviations throughout the rest of the book. There is also a difference
in that DNA and RNA have three of the heterocyclic bases in common,
but one is different. We will return to this in Chapter 2, which deals with
the details of the covalent structures of the nucleic acids.
-Sugar -Phosphate-Sugar-Phosphate-Sugar -Phosphate-Sugar-
I I
Base Base
1
.. . ~~ ~