Transformative Concepts for Drug Design: Target Wrapping

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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.

Author(s): Ariel Fernandez (auth.)
Edition: 1
Publisher: Springer-Verlag Berlin Heidelberg
Year: 2010

Language: English
Pages: 230
Tags: Biomedical Engineering;Medicinal Chemistry;Biophysics and Biological Physics;Cancer Research

Front Matter....Pages i-x
Protein Cooperativity and Wrapping: Two Themes in the Transformative Platform of Molecular Targeted Therapy....Pages 1-15
Wrapping Defects and the Architecture of Soluble Proteins....Pages 17-26
Folding Cooperativity and the Wrapping of Intermediate States of Soluble Natural Proteins....Pages 27-47
Wrapping Deficiencies and De-wetting Patterns in Soluble Proteins: A Blueprint for Drug Design....Pages 49-58
Under-Wrapped Proteins in the Order–Disorder Twilight: Unraveling the Molecular Etiology of Aberrant Aggregation....Pages 59-78
Evolution of Protein Wrapping and Implications for the Drug Designer....Pages 79-96
Wrapping as a Selectivity Filter for Molecular Targeted Therapy: Preliminary Evidence....Pages 97-115
Re-engineering an Anticancer Drug to Make It Safer: Modifying Imatinib to Curb Its Side Effects....Pages 117-140
Wrapping Patterns as Universal Markers for Specificity in the Therapeutic Interference with Signaling Pathways....Pages 141-161
Fulfilling a Therapeutic Imperative in Cancer Treatment: Control of Multi-target Drug Impact....Pages 163-186
Inducing Folding By Crating the Target....Pages 187-196
Wrapper Drugs as Therapeutic Editors of Side Effects....Pages 197-210
Wrapper Drugs for Personalized Medicine....Pages 211-215
Last Frontier and Back to the Drawing Board: Protein–Water Interfacial Tension in Drug Design....Pages 217-223
Back Matter....Pages 225-230