Transformative Concepts for Drug Design: Target Wrapping

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Springer Science & Business Media, 2010 M04 28 - 230 páginas
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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.
 

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This great work by Ariel Fernandez is a pleasure to read and highly rewarding. It covers a lot of ground, from statistical physics to rational drug design, building the scientific foundations of the latter. The book advocates that epistructural biology and not structural biology is truly the supporting field to rationally develop drug designs with therapeutic value. I enthusiastically recommend this book. 

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Ariel Fernandez’ Transformative Concepts for Drug Design is very enjoyable and rewarding. Its conceptual richness , beautiful style, and the breadth of interwoven disciplines, from Statistical Thermodynamics to Molecular Medicine, make it a very valuable and unique asset. The book offers solutions to core problems in Biophysics and will surely leave its mark in the literature as a pioneer foray into the scientific foundations of Molecular Medicine. This is a towering achievement for its breadth and depth of knowledge.  

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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