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

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Chemistry

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Author(s):	Kosuke Ohsawa

Date:	2015	Format:	PDF	Language:	English	ISBN/ASIN:	4431554467
Pages:	1	OCR:		Quality:		ISBN13:
Uploader:	alex21s	Upload Date:	5/8/2020 8:14:23 PM

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This book focuses on thielocin B1 (TB1), which was found to be an inhibitor of proteinprotein 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 ethersilver 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.

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Tags: Inhibitor Interaction Protein-Protein Synthesis Total

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

Category: Chemistry

Description: Click to see full description

Category:
Chemistry