By Kenneth M. Merz, Dagmar Ringe, Charles H. Reynolds
So much medicinal drugs bind to a essentially outlined macromolecular goal that's complementary by way of constitution and chemistry. This remark is the fundamental paradigm of structure-based ligand layout. even though this technique first emerged within the Nineteen Eighties, it has already turn into a strong device for pharmaceutical learn. a lot has been realized, besides the fact that, because the first makes an attempt to find medicinal drugs at the foundation of accessible biochemical and structural info. these days, structure-based ligand layout is a longtime approach for growing medications with new structural positive factors, for enhancing binding actions and pharmacokinetic homes, and for elucidating binding modes and structure-activity relationships.
This quantity offers the underlying rules of the strategy and highlights real-life purposes equivalent to the invention of HIV-protease inhibitors. It indicates that structure-based ligand layout has many merits over different extra conventional ways to designing new medicines, delivering it truly is hired adequately and with an intensive wisdom of the pitfalls to avoid.
the simple presentation and vast checklist of references to the unique literature in addition to a number of colour figures illustrating structural relationships make this quantity an essential instrument for each scientist operating within the quarter of drug discovery.
Chapter 1 Rational layout of Bioactive Molecules (pages 1–13): ok. Gubernator and H.?J. Bohm
Chapter 2 Examples of lively parts of constitution Based?Design (pages 15–36): ok. Gubernator and H.?J. Bohm
Chapter three Structure?Based layout: From Renin to HIV?1 Protease (pages 37–71): Elizabeth A. Lunney and Christine Humblet
Chapter four Zinc Endoproteases: A Structural Superfamily (pages 73–88): N. Borkakoti
Chapter five Structure?Based layout of powerful Beta?Lactamase Inhibitors (pages 89–103): okay. Gubernator, I. Heinze?Krauss, P. Angehrn, R. L. Charnas, C. Hubschwerlen, C. Oefner, M.G.P. web page and F. ok. Winkler
Chapter 6 Inhibition of Sialidase (pages 105–119): Neil R. Taylor
Chapter 7 Rational layout of Inhibitors of HIV?1 opposite Transcriptase (pages 121–127): Wolfgang Schafer
Chapter eight New Computational methods to foretell Protein?Ligand Interactions (pages 129–142): Hans?Joachim Bohm
Chapter nine the way forward for Structure?Based layout: A invaluable principle? (pages 143–147): H.?J. Bohm and okay. Gubernator
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Additional info for Structure-Based Ligand Design
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Hydrogen bonding scheme observed in five X-ray structures of endothiapepsin bound with renin inhibitors . (1111) Non-conserved hydrogen bond; (---)conserved hydrogen bonds. the known extended peptide-like bound conformations. Target inhibitors were docked in the renin active site and evaluated for steric contacts, polar interactions and overall compatibility with the enzyme binding cavity. The rational design approaches applied concepts from peptide mimetics, transition-state replacements, and structural elements extracted from known crystal structures.
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Structure-Based Ligand Design by Kenneth M. Merz, Dagmar Ringe, Charles H. Reynolds