New PDF release: Protein Surface Recognition: Approaches for Drug Discovery

By Ernest Giralt, Mark Peczuh, Xavier Salvatella

ISBN-10: 0470059052

ISBN-13: 9780470059050

A brand new standpoint at the layout of molecular therapeutics is rising. This new procedure emphasizes the rational complementation of performance alongside prolonged patches of a protein floor with the purpose of inhibiting protein/protein interactions. The profitable improvement of compounds in a position to inhibit those interactions bargains a special likelihood to selectively interfere in quite a few key mobile methods relating to human disease.Protein floor reputation offers a close remedy of this procedure, with themes including:an prolonged survey of protein-protein interactions which are key avid gamers in human sickness and biology and the possibility of therapeutics derived from this new perspectivethe basic actual concerns that encompass protein-protein interactions that needs to be thought of while designing ligands for protein surfacesexamples of protein surface-small molecule interactions, together with remedies of protein-natural product interactions, protein-interface peptides, and rational methods to protein floor reputation from version to organic systemsa survey of options that might be necessary to the invention of latest small molecule protein floor binders, from excessive throughput synthesis and screening options to in silico and in vitro equipment for the invention of novel protein ligands.Protein floor popularity offers an highbrow “tool-kit” for investigators in medicinal and bioorganic chemistry trying to make the most this rising paradigm in drug discovery.

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Extra info for Protein Surface Recognition: Approaches for Drug Discovery

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Comb Chem High Throughput Screen 2:125–138. 9. Morrison KL, Weiss GA (2001) Combinatorial alanine-scanning. Curr Opin Chem Biol 5:302–307. 10. Kotz JD, Bond CJ, Cochran AG (2004) Phage-display as a tool for quantifying protein stability determinants. Eur J Biochem 271:1623–1629. 11. Pal G, Kouadio JL, Artis DR, Kossiakoff AA, Sidhu SS (2006) Comprehensive and quantitative mapping of energy landscapes for protein–protein interactions by rapid combinatorial scanning. J Biol Chem 281:22378–22385.

37. You X. et al. (2006) Intracellular protein interaction mapping with FRET hybrids. Proc Natl Acad Sci USA 103:18458–18463. 38. Esposito A, Dohm CP, B€ahr M, Wouters FS (2007) Unsupervised fluorescence lifetime imaging microscopy for high content and high throughput screening. Mol Cell Proteomics 6:1446–1454. 39. Hink MA, Bisselin T, Visser AJ (2002) Imaging protein–protein interactions in living cells. Plant Mol Biol 50:871–883. 20 Protein Surface Recognition 40. Alber F. et al. (2007) Determining the architectures of macromolecular assemblies.

However, it was not until the cloning and expression of the green fluorescent protein (GFP) from the jellyfish Aequorea victoria and its variants [30, 31] that the possibility of utilizing FRET to study protein–protein interactions in vivo became a reality [32, 33]. The use of GFPs is now well established for imaging protein complexes but the size of this protein (27 KDa) makes it desirable to design new tools, such as genetic tags with small dyes [34, 35], to fluorescently label proteins in the cellular environment.

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Protein Surface Recognition: Approaches for Drug Discovery by Ernest Giralt, Mark Peczuh, Xavier Salvatella

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