17451-18-2Relevant articles and documents
Allosteric Inhibition of the Tumor-Promoting Interaction between Exon 2–Depleted Splice Variant of Aminoacyl–Transfer RNA Synthetase-Interacting Multifunctional Protein 2 and Heat Shock Protein 70
Huddar, Srigouri,Kim, Dae Gyu,Kim, Minkyoung,Kim, Sunghoon,Kong, Jiwon,Lee, Kyeong,Lee, Seungbeom,Lee, Sunkyung,Lee, Yuno,Lim, Semi,Park, Chul Min,Suh, Young-Ger
, p. 358 - 371 (2021/12/29)
Although protein-protein interactions (PPIs) have emerged as an attractive therapeutic target space, the identification of chemicals that effectively inhibit PPIs remains challenging. Here, we identified through library screening a chemical probe (compound 1) that can inhibit the tumor-promoting interaction between the oncogenic factor exon 2–depleted splice variant of aminoacyl–transfer RNA synthetase-interacting multifunctional protein 2 (AIMP2-DX2) and heat shock protein 70 (HSP70). We found that compound 1 binds to the N-terminal subdomain of glutathione S-transferase (GST-N) of AIMP2-DX2, causing a direct steric clash with HSP70 and an intramolecular interaction between the N-terminal flexible region and the GST-N of AIMP2-DX2, which induces masking of the HSP70 binding region during molecular dynamics and mutation studies. Compound 1 thus interferes with the AIMP2-DX2 and HSP70 interaction and suppresses the growth of cancer cells that express high levels of AIMP2-DX2 in vitro and in preliminary in vivo experiment. This work provides an example showing that allosteric conformational changes induced by chemicals can be a way to control pathologic PPIs. SIGNIFICANCE STATEMENT Compound 1 is a promising protein-protein interaction inhibitor between AIMP2-DX2 and HSP70 for cancer therapy by the mechanism with allosteric modulation as well as competitive binding. It seems to induce allosteric conformational change of AIMP2-DX2 proteins and direct binding clash between AIMP2-DX2 and HSP70. The compound reduced the level of AIMP2-DX2 in ubiquitin-dependent manner via suppression of binding between AIMP2-DX2 and HSP70 and suppressed the growth of cancer cells highly expressing AIMP2-DX2 in vitro and in preliminary in vivo experiment.
The Employment of Sodium Hydride as a Michael Donor in Palladium-catalyzed Reductions of α, β-Unsaturated Carbonyl Compounds
Liu, Ye,Mao, Yujian,Hu, Yanwei,Gui, Jingjing,Wang, Liang,Wang, Wei,Zhang, Shilei
supporting information, p. 1554 - 1558 (2019/02/16)
Sodium hydride was employed as a Michael donor under the catalysis of PdCl2 for 1,4-conjugate reductions of α, β-unsaturated carbonyl compounds, which features operational simplicity, mild conditions and high atom-economy. The merits of NaH as a reductant were demonstrated by the one-pot or cascade reactions for the syntheses of complex molecules. (Figure presented.).
A Novel Synthesis of Some 1,4-Phenylene-bis-heterocyclic Derivatives and of Some Pyran, Pyrano[2,3-c]pyrazole, and Pyrano[2,3-d]pyrimidine Derivatives [1]
Abdelrazek,Helal,Hebishy,Hassan
, p. 1026 - 1031 (2015/08/06)
p-Diacetyl benzene 1 undergoes bromination to afford p-bromoacetyl phenacyl bromide 2. Compound 2 reacts with twofold excess of malononitrile to afford 2-{2-[4-(3,3-Dicyanopropionyl)-phenyl]-2-oxo-ethyl}-malononitrile 3. Compound 3 could be cyclized to af
