Transformative Concepts for Drug Design: Target WrappingSpringer 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
| 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 | 48 |
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 | 162 |
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 | 224 |
| 227 | |
9 Wrapping Patterns as Universal Markers for Specificity in the Therapeutic Interference with Signaling Pathways | 141 |
Otras ediciones - Ver todas
Transformative Concepts for Drug Design: Target Wrapping Ariel Fernandez Sin vista previa disponible - 2010 |
Transformative Concepts for Drug Design: Target Wrapping Ariel Fernandez Sin vista previa disponible - 2014 |
Términos y frases comunes
Acad Sci USA affinity alignment amide and carbonyl anticancer assay association backbone hydrogen bonds Bcr-Abl binding bioinformatics Brc-Abl C-Kit C-Kit kinase cancer cardiotoxicity cells Chap chapter Chem chemotype complex conformation conserved copyright 2007 correlation crating cross-reactivity de-wetting hot spots dehydration propensity dehydron dehydron patterns desolvation domain dielectric disulfide disulfide bonds dosage imbalance drug design dynamics EGFR electrostatic Fernández gene Gleevec high-throughput screening homolog human hydration hydrophobic collapse imatinib inhibition inhibitory impact interactions interfacial water intramolecular hydrogen bonds kinase inhibitors kinome ligand methylation microenvironment miRNA Mol Biol molecular MST2 Natl Acad Sci nonpolar nonpolar groups packing defects paired paralogs pathway PDB-reported PDGFR peptide phosphorylation predicted Proc Natl Acad promiscuous promote protein folding regions residues selectivity filter shown side chain side effects soluble proteins solvent sorafenib specificity staurosporine structural deficiencies SUDE sunitinib target protein therapeutic therapy tumor tyrosine kinase ubiquitin under-wrapping water molecules WBZ_4 well-wrapped wrapper wrapping patterns
