rdf-syntax-grammar
mods:
  schema location: http://www.loc.gov/mods/v3 http://www.loc.gov/standards/mods/v3/mods-3-2.xsd
  title info:
    title: Total Synthesis of Thielocin B1 as a Protein-Protein Interaction Inhibitor of PAC3 Homodimer
  name:
    name part: Ohsawa, Kosuke.
    role:
      role term: creator
    role:
      role term: author.
  name:
    name part: SpringerLink (Online service)
  type of resource: text
  origin info:
    place:
      place term: ja
    date issued: 2015
    issuance: monographic
  language:
    language term: eng
  physical description:
    form: electronic
    form: electronic resource
    reformatting quality: access
    form: remote
    extent: XIII, 109 p. 84 illus., 14 illus. in color. online resource.
  abstract: 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.
  table of contents: 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.
  note: by Kosuke Ohsawa.
  subject:
    topic: Chemistry
  subject:
    topic: Pharmacy
  subject:
    topic: Organic chemistry
  subject:
    topic: Medicinal chemistry
  subject:
    topic: Chemistry
  subject:
    topic: Organic Chemistry
  subject:
    topic: Pharmacy
  subject:
    topic: Medicinal Chemistry
  classification: QD415-436
  classification: 547
  related item:
    title info:
      title: Springer eBooks
  related item:
    title info:
      title: Springer Theses, Recognizing Outstanding Ph.D. Research
  identifier: 9784431554479
  identifier: http://dx.doi.org/10.1007/978-4-431-55447-9
  record info:
    record creation date: 150113
    record change date: 20151204173454.0
    record identifier: 978-4-431-55447-9