927801-29-4Relevant academic research and scientific papers
Developing Inhibitors of the p47phox-p22phox Protein-Protein Interaction by Fragment-Based Drug Discovery
Solbak, Sara Marie ?ie,Zang, Jie,Narayanan, Dilip,H?j, Lars Jakobsen,Bucciarelli, Saskia,Softley, Charlotte,Meier, Sebastian,Langkilde, Annette Eva,Gotfredsen, Charlotte Held,Sattler, Michael,Bach, Anders
, p. 1156 - 1177 (2020/03/10)
Nicotinamide adenine dinucleotide phosphate oxidase isoform 2 is an enzyme complex, which generates reactive oxygen species and contributes to oxidative stress. The p47phox-p22phox interaction is critical for the activation of the catalytical NOX2 domain, and p47phox is a potential target for therapeutic intervention. By screening 2500 fragments using fluorescence polarization and a thermal shift assay and validation by surface plasmon resonance, we found eight hits toward the tandem SH3 domain of p47phox (p47phoxSH3A-B) with KD values of 400-600 μM. Structural studies revealed that fragments 1 and 2 bound two separate binding sites in the elongated conformation of p47phoxSH3A-B and these competed with p22phox for binding to p47phoxSH3A-B. Chemical optimization led to a dimeric compound with the ability to potently inhibit the p47phoxSH3A-B-p22phox interaction (Ki of 20 μM). Thereby, we reveal a new way of targeting p47phox and present the first report of drug-like molecules with the ability to bind p47phox and inhibit its interaction with p22phox.
Recyclable catalysts for palladium-catalyzed aminations of aryl halides
Dumrath, Andreas,Luebbe, Christa,Neumann, Helfried,Jackstell, Ralf,Beller, Matthias
experimental part, p. 9599 - 9604 (2011/10/04)
Aminated and recycled: Palladium/imidazolium phosphane catalysts enable efficient and general aminations of aryl halides, including direct amination with ammonia. Subsequent recycling is possible without any additional heterogenization (see scheme).
Recyclable catalysts for palladium-catalyzed C - O coupling reactions, Buchwald-Hartwig aminations, and Sonogashira reactions
Dumrath, Andreas,Wu, Xiao-Feng,Neumann, Helfried,Spannenberg, Anke,Jackstell, Ralf,Beller, Matthias
supporting information; experimental part, p. 8988 - 8992 (2011/02/23)
Simply reuse: Homogeneous palladium catalysts are effective and attractive tools for advanced organic synthesis (see example). Compound 1 belongs to a new class of ligands that enable recycling of the precious-metal catalyst directly from the reaction without any heterogenization.
