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作者 Ohsawa, Kosuke, author
書名 Total synthesis of thielocin B1 as a protein-protein interaction inhibitor of PAC3 homodimer / by Kosuke Ohsawa
出版項 Tokyo : Springer Japan : Imprint: Springer, 2015
國際標準書號 9784431554479 (electronic bk.)
9784431554462 (paper)
國際標準號碼 10.1007/978-4-431-55447-9 doi
book jacket
說明 1 online resource (xiii, 109 pages) : illustrations (some color), digital ; 24 cm
text txt rdacontent
computer c rdamedia
online resource cr rdacarrier
text file PDF rda
系列 Springer theses, 2190-5053
Springer theses
附註 Introduction -- 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
This 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
Host Item Springer eBooks
主題 Proteins -- Inhibitors
Protein-protein interactions
Organic Chemistry
Medicinal Chemistry
Alt Author SpringerLink (Online service)
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