Total Synthesis of Thielocin B1 as a Protein-Protein Interaction Inhibitor of PAC3 Homodimer

Language: English

Published by Springer, Springer Jan 2015, 2015

4431554467 / 9784431554462

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This item is printed on demand - Print on Demand Titel. Neuware -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.Springer-Verlag KG, Sachsenplatz 4-6, 1201 Wien 124 pp. Englisch.…

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Title
Total Synthesis of Thielocin B1 as a Protein-Protein Interaction Inhibitor of PAC3 Homodimer
Author
Kosuke Ohsawa
Publisher
Springer, Springer Jan 2015
Publication year
2015
Condition
Neu
Binding
Buch
Language
English
ISBN 10
4431554467
ISBN 13
9784431554462
Item weight
360 grams
Dimensions
241x160x13 mm

buchversandmimpf2000

Emtmannsberg, BAYE, Germany

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