Description
Driving further the research on mammalian alkaline phosphatase structure and function, Phosphatase Modulators collects expert contributions into one “how to” manual for basic scientists interested in initiating a drug discovery effort. While this book contains the traditional method chapters and some typical reviews on the structure and known functions of phosphatases, other contributions are meant to discuss approaches and alternatives useful in making “go/no-go” decisions in high throughput screening (HTS) and lead optimization campaigns. Many chapters focus on tissue-nonspecific alkaline phosphatase (TNAP) as well as protein phosphatases. Written for the highly successful Methods in Molecular Biology series, chapters in this volume include the kind of detail and key implementation advice that promotes reproducible results. Step-by-step and practical, Phosphatase Modulators offers a path to understanding many of the facets and complexities associated with undertaking a drug discovery effort and will serve as a roadmap to initiating those efforts. 1. Chemical Probe Development Versus Drug Development Michael R. Jackson 2. Phosphatase High-Throughput Screening Assay Design and Selection Eduard A. Sergienko 3. Multisystemic Functions of Alkaline Phosphatases Ren Buchet, Jos Luis Milln, and David Magne 4. Robotic Implementation of Assays: Tissue-Nonspecific Alkaline Phosphatase (TNAP) Case Study Thomas D.Y. Chung 5. Inhibitors of Tissue-Nonspecific Alkaline Phosphatase (TNAP): From Hits to Leads Peter Teriete, Anthony B. Pinkerton, and Nicholas D.P. Cosford 6. A Method for Direct Assessment of Tissue-Nonspecific Alkaline Phosphatase (TNAP) Inhibitors in Blood Samples Eduard Sergienko, Qing Sun, and Chen-Ting Ma 7. Isolation and Characteristics of Matrix Vesicles Ren Buchet, Slawomir Pikula, David Magne, and Sada Mebarek 8. The Use of Tissue-Nonspecific Alkaline Phosphatase (TNAP) and PHOSPHO1 Inhibitors to Affect Mineralization by Cultured Cells Tina Kiffer-Moreira and Sonoko Narisawa 9. Modulators of Intestinal Alkaline Phosphatase Ekaterina V. Bobkova, Tina Kiffer-Moreira, and Eduard A. Sergienko 10. New Activity Assays for ENPP1 with Physiological Substrates ATP and ADP Chen-Ting Ma and Eduard Sergienko 11. Structure of Acid Phosphatases Csar L. Araujo and Pirkko T. Vihko 12. Purification of Prostatic Acid Phosphatase (PAP) for Structural and Functional Studies Annakaisa M. Herrala, Ileana B. Quintero, and Pirkko T. Vihko 13. Protein Tyrosine Phosphatases: Structure, Function, and Implication in Human Disease Lutz Tautz, David A. Critton, and Stefan Grotegut 14. High-Throughput Screening for Protein Tyrosine Phosphatase Activity Modulators Lutz Tautz and Eduard A. Sergienko 15. Evaluating Effects of Tyrosine Phosphatase Inhibitors on T Cell Receptor Signaling Souad Rahmouni, Laurence Delacroix, Wallace H. Liu, and Lutz Tautz 16. Interactor-Guided Dephosphorylation by Protein Phosphatase-1 Shannah Boens, Kathelijne Szekr, Aleyde Van Eynde, and Mathieu Bollen 17. Structure, Regulation, and Pharmacological Modulation of PP2A Phosphatases Caroline Lambrecht, Dorien Haesen, Ward Sents, Elitsa Ivanova, and Veerle Janssens
