Transformative Concepts for Drug Design: Target Wrapping

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Springer Science & Business Media, 2010 M04 28 - 230 páginas
In spite of the enticing promises of the post-genomic era, the pharmaceutical world is in a state of disarray. Drug discovery seems now riskier and more uncertain than ever. Thus, projects get routinely terminated in mid-stage clinical trials, new targets are getting harder to find, and successful therapeutic agents are often recalled as unanticipated side effects are discovered. Exploiting the huge output of genomic studies to make safer drugs has proven to be much more difficult than anticipated. More than ever, the lead in the pharmaceutical industry depends on the ability to harness innovative research, and this type of innovation can only come from one source: fundamental knowledge. This book squarely addresses this crucial problem since it introduces fundamental discoveries in basic biomolecular research that hold potential to broaden the technological base of the pharmaceutical industry. The book takes a fresh and fundamental look at the problem of how to design an effective drug with controlled specificity. Since the novel transformative concepts are unfamiliar to most practitioners, the first part of this book explains matters very carefully starting from a fairly elementary physico-chemical level. The second part of the book is devoted to practical applications, aiming at nothing less than a paradigm shift in drug design. This book is addressed to scientists working at the cutting edge of research in the pharmaceutical industry, but the material is at the same time accessible to senior undergraduates or graduate students interested in drug discovery and molecular design.
 

Contenido

Two Themes in the Transformative Platform of Molecular Targeted Therapy
1
2 Wrapping Defects and the Architecture of Soluble Proteins
17
3 Folding Cooperativity and the Wrapping of Intermediate States of Soluble Natural Proteins
27
A Blueprint for Drug Design
49
Unraveling the Molecular Etiology of Aberrant Aggregation
59
6 Evolution of Protein Wrapping and Implications for the Drug Designer
79
Preliminary Evidence
97
Modifying Imatinib to Curb Its Side Effects
117
Control of Multitarget Drug Impact
163
11 Inducing Folding By Crating the Target
187
12 Wrapper Drugs as Therapeutic Editors of Side Effects
197
13 Wrapper Drugs for Personalized Medicine
211
ProteinWater Interfacial Tension in Drug Design
217
Epilogue
225
Index
227
Derechos de autor

9 Wrapping Patterns as Universal Markers for Specificity in the Therapeutic Interference with Signaling Pathways
141

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