Applying Genomic And Proteomic Microarray Technology In Drug Discovery.pdf

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APPLYING GENOMIC
AND
PROTEOMIC MICROARRAY
TECHNOLOGY
IN
DRUG DISCOVERY
Copyright 2005 by CRC Press
APPLYING GENOMIC
AND
PROTEOMIC MICROARRAY
TECHNOLOGY
IN
DRUG DISCOVERY
Robert S. Matson
CRC PR E S S
Boca Raton London New York Washington, D.C.
Copyright 2005 by CRC Press
Library of Congress Cataloging-in-Publication Data
Matson, Robert S.
Applying genomic and proteomic microarray technology in drug discovery /
Robert S. Matson.
p. ; cm.
Includes bibliographical references.
ISBN 0-8493-1469-0
1. High throughput screening (Drug development) 2. DNA microarrays. 3. Protein
microarrays. 4. Pharmacogenomics. 5. Proteomics.
[DNLM: 1. Drug Design. 2. Genomics--methods. 3. Oligonucleotide Array Sequence
Analysis--methods. 4. Proteomics--methods. QV 744 M434a 2004] I. Title.
RS419.5.M38 2004
615'.19--dc22
2004057042
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Library of Congress Card Number 2004057042
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Copyright 2005 by CRC Press
Preface
Array technology, much like polymerase chain reaction (PCR) technique,
was created to satisfy an existing need in molecular biology. PCR provided
a means to amplify enough DNA to sequence genes. The first applications
for arrays involved gene sequencing by hybridization (SBH) and genotyping.
However, gel-based sequencing quickly supplanted the emerging SBH
approach, while genotyping and mutation analysis have been slow in devel-
opment. The challenge for those involved in array technology then became
finding that elusive application niche, one that would demonstrate a clear,
unmitigated, and thereby sustained need for the technology.
This book picks up the array technology journey from the mid-1990s
with the introduction of microarray-based gene expression analysis. The
global analysis of genes by microarrays has provided a fresh and exciting
view of the cellular process. More importantly, it enabled others to consider
similar utility in various “omic” fields. Hence, we have witnessed the emer-
gence of protein arrays to address proteomics.
In writing this book, my aim was first to provide a detailed description
and offer insight into present and future utilities for microarray technology.
While arguably array-based technologies are now being adopted in diverse
fields, I have placed emphasis on applications related to drug discovery.
Microarrays continue to play significant and increasingly important roles in
the drug discovery process.
Chapter 1
considers the respective roles as well as the many issues
surrounding the future adoption of gene expression and protein microarrays
for pharmacogenomic and pharmacoproteomic applications. For acceptance
by the pharmaceutical and diagnostic industries, commercially validated
array technology is required.
Chapter 2
details the commercial microarray
landscape.
Chapter 3
describes alternative substrates and the preparation of
various surface chemistries along with their suitability for immobilization
of nucleic acids and proteins. In
Chapter 4,
the mechanics of microarraying
are described in detail including environmental conditions, printer and pin
performance, and instructions for setting up a print run. Protocols for print-
ing nucleic acids and proteins are provided along with in-depth discussion
of other important parameters such as print buffers (inks) and factors influ-
encing print quality. I also set out to discuss the importance and provide a
critical assessment of studies that helped to define applications in genomics
Copyright 2005 by CRC Press
and proteomics. In
Chapter 5,
gene expression microarray applications are
described;
Chapter 6
examines the utility of protein microarrays.
Finally, an understanding of the making of a microarray is fundamen-
tally important to those interested in producing “spotted” arrays and prop-
erly using them. While complementary (cDNA) microarray fabrication on
glass slides has been well studied, we have less experience with the attach-
ment of oligonucleotides and the preparation of protein arrays. Moreover,
additional substrates and surface chemistries that may be better suited for
printing proteins are now available.
It is my hope that this book will provide you with the knowledge and
confidence to embrace microarraying in your future.
Robert S. Matson, Ph.D.
Orange, California
Copyright 2005 by CRC Press

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