Is NMR Fragment Screening Fine-Tuned to Assess Druggability of Protein-Protein Interactions? was written by Dias, David M.;Van Molle, Inge;Baud, Matthias G. J.;Galdeano, Carles;Geraldes, Carlos F. G. C.;Ciulli, Alessio. And the article was included in ACS Medicinal Chemistry Letters in 2014.Related Products of 19668-85-0 This article mentions the following:
Modulation of protein-protein interactions (PPIs) with small mols. has been hampered by a lack of lucid methods capable of reliably identifying high-quality hits. In fragment screening, the low ligand efficiencies associated with PPI target sites pose significant challenges to fragment binding detection. Here, we investigate the requirements for ligand-based NMR techniques to detect rule-of-three compliant fragments that form part of known high-affinity inhibitors of the PPI between the von Hippel-Lindau protein and the alpha subunit of hypoxia-inducible factor 1 (pVHL:HIF-1α). Careful triaging allowed rescuing weak but specific binding of fragments that would otherwise escape detection at this PPI. Further structural information provided by saturation transfer difference (STD) group epitope mapping, protein-based NMR, competitive isothermal titration calorimetry (ITC), and X-ray crystallog. confirmed the binding mode of the rescued fragments. Our findings have important implications for PPI druggability assessment by fragment screening as they reveal an accessible threshold for fragment detection and validation. In the experiment, the researchers used many compounds, for example, 3-Methylisoxazole-5-acetic Acid (cas: 19668-85-0Related Products of 19668-85-0).
3-Methylisoxazole-5-acetic Acid (cas: 19668-85-0) belongs to isoxazole derivatives. Isoxazoles are aromatic heterocycles containing an N–O bond. The weakness of this bond allows the ring opening of these heterocycles under reductive conditions. The most common methods for N–O bond cleavage in isoxazoles are hydrogenation with palladium or platinum catalysts or with Raney Ni. Recent developments have shown that Mo(CO)6 efficiently cleaves the N–O bond in isoxazoles.Related Products of 19668-85-0
Referemce:
Isoxazole – Wikipedia,
Isoxazole | C3H3NO – PubChem