Total Synthesis of Thielocin B1 as a Protein-Protein Interaction Inhibitor of PAC3 Homodimer - Springer Theses (Hardback)
  • Total Synthesis of Thielocin B1 as a Protein-Protein Interaction Inhibitor of PAC3 Homodimer - Springer Theses (Hardback)
zoom

Total Synthesis of Thielocin B1 as a Protein-Protein Interaction Inhibitor of PAC3 Homodimer - Springer Theses (Hardback)

(author)
£99.99
Hardback 109 Pages / Published: 26/01/2015
  • We can order this

Usually dispatched within 3 weeks

  • This item has been added to your basket

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.

Publisher: Springer Verlag, Japan
ISBN: 9784431554462
Number of pages: 109
Weight: 387 g
Dimensions: 235 x 155 x 8 mm
Edition: 2015 ed.

You may also be interested in...

Please sign in to write a review

Your review has been submitted successfully.