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OverviewThis book focuses on thielocin B1 (TB1), which was found to be an inhibitor of protein–protein interactions (PPIs) of proteasome assembling chaperone (PAC) 3 homodimer, and elucidates the mechanism by nuclear magnetic resonance (NMR) studies. Interfaces of PPIs recently have been expected to be novel therapeutic targets, while it is difficult to apply conventional methodology based on lock and key theory. The author achieved the first total synthesis of TB1 and its spin-labeled derivative to carry out NMR experiments because the supply of TB1 from natural sources was limited. Unique 2,2’,6,6’-tetrasubstituted diphenyl ether moiety of TB1 was synthesized from a depsidone skeleton by chemoselective reduction of lactone. In the process of elongating side wings, efficient formylation utilizing dichloromethyl methyl ether–silver trifluoromethanesulfonate was developed for the sterically hindered aromatic compound. NMR titration experiments and paramagnetic relaxation enhancement observation of PAC3 homodimer were performed with synthesized TB1 and its molecular probe, respectively. The results of the above NMR studies and additional in silico docking studies suggested that TB1 promotes the dissociation to monomeric PAC3 after interaction with PAC3 homodimer. The rare mechanism shown in this book indicates a potential novel drug target in the interfaces of PPIs with no cavity or groove. Full Product DetailsAuthor: Kosuke OhsawaPublisher: Springer Verlag, Japan Imprint: Springer Verlag, Japan Edition: 2015 ed. Dimensions: Width: 15.50cm , Height: 0.80cm , Length: 23.50cm Weight: 0.454kg ISBN: 9784431554462ISBN 10: 4431554467 Pages: 109 Publication Date: 26 January 2015 Audience: Professional and scholarly , Professional & Vocational Format: Hardback Publisher's Status: Active Availability: Manufactured on demand  We will order this item for you from a manufactured on demand supplier. Table of ContentsIntroduction.- Total Synthesis of Thielocin B1 and NMR Chemical Shift Perturbation Experiments with PAC3 Homodimer.- Synthesis of Spin-labeled Thielocin B1 and Observation of Paramagnetic Relaxation Enhancement Effects.- An Improved Method for the Direct Formylation ob Substituted Benzenes Using Dichloromethyl Methyl Ether-Silver Trifluoromethanesulfonate.- Conclusions.ReviewsAuthor InformationTab Content 6Author Website:Countries AvailableAll regions |
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