Sets the stage for advances in drug discovery using the
latest enzyme technology

Reviewing new and emerging applications of enzyme technology in
drug discovery, this book highlights some of the most promising
areas of pharmaceutical and biotechnology research. It covers
enzyme assay technology, utilization of enzymology for prodrug
design, and the application of enzymes as therapeutic agents.
Expert reviews highlight how our latest understanding of enzymology
is used to develop new practical applications in drug discovery and
design.

Filled with case studies, Enzyme Technologies: Pluripotent
Players in Discovering Therapeutic Agents enables readers to
better understand the diverse functions of enzymes and master
specific applications in drug discovery research. In addition to
small molecule drug discovery, the book explores new developments
in enzymes as therapeutic agents for genetic disorders.

* Section A, Enzymes - Essential Workhorses in
Pharmaceutical Research, offers support in selecting the best
enzyme targets for drug discovery, designing enzyme inhibitors for
therapeutic agents, and evaluating selective enzyme
inhibitors.

* Section B, Enzymes - Indispensable Tools for Improving
Druggability, sets forth the principles alongside real-world
examples of exploiting specific properties of enzymes to design
successful prodrugs.

* Section C, Enzymes - Powerful Weapons for Correcting
Nature's Errors, provides new insights on applying enzymes as
therapeutic agents or diagnostic tools to treat genetic
disorders.

Chapters are contributed by leading experts from around the
world. Their contributions are based on a thorough review of the
current literature as well as their own research.

Reviewing our latest understanding of the nature of enzymes and
their role in drug discovery, this book is recommended for
researchers in pharmaceuticals and biotechnology as well as for
researchers in enzymology, biochemistry, molecular biology, and
medicinal chemistry.

HSIU-CHIUNG YANG, PhD, is Research Advisor at Eli Lilly
and Company. She is the author or coauthor of over forty
publications and holder of two patents.

WU-KUANG YEH, PhD, is Adjunct Professor at Indiana
University Purdue University Indianapolis (IUPUI), and was Director
of Research and Principal Investigator at PreClinOmics, Inc. The
holder of six U.S. patents, Dr. Yeh is the author or coauthor of
over 115 publications.

JAMES R. McCARTHY, PhD, is Research Professor in the
department of chemistry and chemical biology at Indiana University
Purdue University Indianapolis (IUPUI), and was a Distinguished
Research Fellow at Eli Lilly and Company. He is the author or
coauthor of over 130 publications and holder of over sixty
patents.

Sets the stage for advances in drug discovery using the latest enzyme technology

Reviewing new and emerging applications of enzyme technology in drug discovery, this book highlights some of the most promising areas of pharmaceutical and biotechnology research. It covers enzyme assay technology, utilization of enzymology for prodrug design, and the application of enzymes as therapeutic agents. Expert reviews highlight how our latest understanding of enzymology is used to develop new practical applications in drug discovery and design.

Filled with case studies, Enzyme Technologies: Pluripotent Players in Discovering Therapeutic Agents enables readers to better understand the diverse functions of enzymes and master specific applications in drug discovery research. In addition to small molecule drug discovery, the book explores new developments in enzymes as therapeutic agents for genetic disorders.

• Section A, Enzymes – Essential Workhorses in Pharmaceutical Research, offers support in selecting the best enzyme targets for drug discovery, designing enzyme inhibitors for therapeutic agents, and evaluating selective enzyme inhibitors.
• Section B, Enzymes – Indispensable Tools for Improving Druggability, sets forth the principles alongside real-world examples of exploiting specific properties of enzymes to design successful prodrugs.
• Section C, Enzymes – Powerful Weapons for Correcting Nature's Errors, provides new insights on applying enzymes as therapeutic agents or diagnostic tools to treat genetic disorders.

Chapters are contributed by leading experts from around the world. Their contributions are based on a thorough review of the current literature as well as their own research.

Reviewing our latest understanding of the nature of enzymes and their role in drug discovery, this book is recommended for researchers in pharmaceuticals and biotechnology as well as for researchers in enzymology, biochemistry, molecular biology, and medicinal chemistry.

Contributors vii

Preface ix

Part A _Enzymes - essential workhorses in
pharmaceutical research 1

1 Assay Technologies for Proteases 3

Anuradha Roy, Gerald H. Lushington, James McGee, and Rathnam
Chaguturu

2 Discovery and Development of Isozyme-Selective Inhibitors
Involved in Lipid Metabolism 55

Taichi Ohshiro and Hiroshi Tomoda

3 Covalent Enzyme Inhibition in Drug Discovery and Development
81

Shujaath Mehdi

4 Preclinomics: Enzyme Assays and Rodent Models for Metabolic
diseases 131

Wu-Kuang Yeh and Richard G. Peterson

Part B _Enzymes - indispensable tools for
improving druggability 163

5 Enzymes and Targeted Activation of Prodrugs 165

Yanhui Yang, Yu Chen, Herve Aloysius, Daigo Inoyama, and Longqin
Hu

6 Evolution of an Orally Active Prodrug of Gemcitabine 237

James R. McCarthy

7 Enzymatically Activated Phosphate and Phosphonate Prodrugs
253

Ivan S. Krylov and Charles E. McKenna

Part C E nzymes - powerful weapons for correcting
Nature's errors 301

8 Treatment Options for Mucopolysaccharidosis Type II
(Hunter's Syndrome) 303

Michael Beck

9 Enzyme Replacement Therapy for Fabry Disease 321

Ley Nadine Lacbawan, Wei Zheng, and Ozlem Goker-Alpan

10 Methods and Principles of Pancreatic Function Tests 335

Henrike von Schassen, Jutta Keller, and Peter Layer

Index 341