Enzyme Technologies (eBook)

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.

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

"The book serves as a valuable desk reference volume and describes well the key concepts of the standard and emerging enzyme technologies that together constitute some of the fundamental principles and knowledge on which drug discovery research is based." (ChemMedChem, 1 August 2015)