Proteomics in Drug Research Book

A Personal Foreword.

Preface.

List of Contributors.

I Introduction.

1 Administrative Optimization of Proteomics Networks for Drug Development (André van Hall and Michael Hamacher).

1.1 Introduction.

1.2 Tasks and Aims of Administration.

1.3 Networking.

1.4 Evaluation of Biomarkers.

1.5 A Network for Proteomics in Drug Development.

1.6 Realization of Administrative Networking: the Brain Proteome Projects.

References.

2 Proteomic Data Standardization, Deposition and Exchange (Sandra Orchard, Henning Hermjakob, Manuela Pruess, and Rolf Apweiler).

2.1 Introduction.

2.2 Protein Analysis Tools.

2.3 Data Storage and Retrieval.

2.4 The Proteome Standards Initiative.

2.5 General Proteomics Standards (GPS).

2.6 Mass Spectrometry.

2.7 Molecular Interactions.

2.8 Summary.

References.

II Proteomic Technologies.

3 Difference Gel Electrophoresis (DIGE): the Next Generation of Two-Dimensional Gel Electrophoresis for Clinical Research (Barbara Sitek, Burghardt Scheibe, Klaus Jung, Alexander Schramm and Kai Stühler).

3.1 Introduction.

3.2 Difference Gel Electrophoresis: Next Generation of Protein Detection in 2-DE.

References.

4 Biological Mass Spectrometry: Basics and Drug Discovery Related Approaches (Bettina Warscheid).

4.1 Introduction.

4.2 Ionization Principles.

4.3 Mass Spectrometric Instrumentation.

4.4 Protein Identification Strategies.

4.5 Quantitative Mass Spectrometry for Comparative and Functional Proteomics.

4.6 Metabolic Labeling Approaches.

4.7 Chemical Labeling Approaches.

4.8 Quantitative MS for Deciphering Protein–Protein Interactions.

4.9 Conclusions.

References.

5 Multidimensional Column Liquid Chromatography (LC) in Proteomics – Where Are We Now? (Egidijus Machtejevas, Klaus K. Unger and Reinhard Ditz).

5.1 Introduction.

5.2 Why Do We Need MD-LC/MS Methods?

5.3 Basic Aspects of Developing a MD-LC/MS Method.

5.4 Applications of MD-LC Separation in Proteomics – a Brief Survey.

5.5 Sample Clean-Up: Ways to Overcome the “Bottleneck” in Proteome Analysis.

5.6 Summary.

References.

6 Peptidomics Technologies and Applications in Drug Research (Michael Schrader, Petra Budde, Horst Rose, Norbert Lamping, Peter Schulz-Knappe and Hans-Dieter Zucht).

6.1 Introduction.

6.2 Peptides in Drug Research.

6.3 Development of Peptidomics Technologies.

6.4 Applications of Differential Display Peptidomics.

6.5 Outlook.

References.

7 Protein Biochips in the Proteomic Field (Angelika Lücking and Dolores J. Cahill).

7.1 Introduction.

7.2 Technological Aspects.

7.3 Applications of Protein Biochips.

7.4 Contribution to Pharmaceutical Research and Development.

References.

8 Current Developments for the In Vitro Characterization of Protein Interactions (Daniela Moll, Bastian Zimmermann, Frank Gesellchen and Friedrich W. Herberg).

8.1 Introduction.

8.2 The Model System: cAMP-Dependent Protein Kinase.

8.3 Real-time Monitoring of Interactions Using SPR Biosensors.

8.4 ITC in Drug Design.

8.5 Fluorescence Polarization, a Tool for High-Throughput Screening.

8.6 AlphaScreen as a Pharmaceutical Screening Tool.

8.7 Conclusions.

References.

9 Molecular Networks in Morphologically Intact Cells and Tissue–Challenge for Biology and Drug Development (Walter Schubert, Manuela Friedenberger and Marcus Bode).

9.1 Introduction.

9.2 A Metaphor of the Cell.

9.3 Mapping Molecular Networks as Patterns: Theoretical Considerations.

9.4 Imaging Cycler Robots.

9.5 Formalization of Network Motifs as Geometric Objects.

9.6 Gain of Functional Information: Perspectives for Drug Development.

References.

III Applications.

10 From Target to Lead Synthesis (Stefan Müllner, Holger Stark, Päivi Niskanen, Erich Eigenbrodt, Sybille Mazurek and Hugo Fasold).

10.1 Introduction.

10.2 Materials and Methods.

10.3 Results.

10.4 Discussion.

References.

11 Differential Phosphoproteome Analysis in Medical Research (Elke Butt and Katrin Marcus).

11.1 Introduction.

11.2 Phosphoproteomics of Human Platelets.

11.3 Identification of cAMP- and cGMP-Dependent Protein Kinase Substrates in Human Platelets.

11.4 Identification of a New Therapeutic Target for Anti-Inflammatory Therapy by Analyzing Differences in the Phosphoproteome of Wild Type and Knock Out Mice.

11.5 Concluding Remarks and Outlook.

References.

12 Biomarker Discovery in Renal Cell Carcinoma Applying Proteome-Based Studies in Combination with Serology (Barbara Seliger and Roland Kellner).

12.1 Introduction.

12.2 Rational Approaches Used for Biomarker Discovery.

12.3 Advantages of Different Proteome-Based Technologies for the Identification of Biomarkers.

12.4 Type of Biomarker.

12.5 Proteome Analysis of Renal Cell Carcinoma Cell Lines and Biopsies.

12.6 Validation of Differentially Expressed Proteins.

12.7 Conclusions.

References.

13 Studies of Drug Resistance Using Organelle Proteomics (Catherine Fenselau and Zongming Fu).

13.1 Introduction.

13.2 Objectives and Experimental Design.

13.3 Changes in Plasma Membrane and Nuclear Proteins in MCF-7 Cells Resistant to Mitoxantrone.

References.

14 Clinical Neuroproteomics of Human Body Fluids: CSF and Blood Assays for Early and Differential Diagnosis of Dementia (Jens Wiltfang and Piotr Lewczuk).

14.1 Introduction.

14.2 Neurochemical Markers of Alzheimer’s Disease.

14.3 Conclusions.

References.

15 Proteomics in Alzheimer’s Disease (Michael Fountoulakis, Sophia Kossida and Gert Lubec).

15.1 Introduction.

15.2 Proteomic Analysis.

15.3 Proteins with Deranged Levels and Modifications in AD.

15.4 Limitations.

References.

16 Cardiac Proteomics (Emma McGregor and Michael J. Dunn).

16.1 Heart Proteomics.

16.2 Vessel Proteomics.

16.3 Concluding Remarks.

References.

IV To the Market.

17 Innovation Processes (Sven Rüger).

17.1 Introduction.

17.2 Innovation Process Criteria.

17.3 The Concept.

17.4 Market Attractiveness.

17.5 Competitive Market Position.

17.6 Competitive Technology Position.

17.7 Strengthen the Fit.

17.8 Reward.

17.9 Risk.

17.10 Innovation Process Deliverables for each Stage.

17.11 Stage Gate-Like Process.

17.12 Conclusion.

Subject Index.