Dissecting Fragment-Based Lead Discovery at the von Hippel-Lindau Protein:Hypoxia Inducible Factor 1α Protein-Protein Interface was written by Van Molle, Inge;Thomann, Andreas;Buckley, Dennis L.;So, Ernest C.;Lang, Steffen;Crews, Craig M.;Ciulli, Alessio. And the article was included in Chemistry & Biology (Oxford, United Kingdom) in 2012.Synthetic Route of C6H7NO3 This article mentions the following:
Fragment screening is widely used to identify attractive starting points for drug design. However, its potential and limitations to assess the tractability of often challenging protein:protein interfaces have been underexplored. Here, we address this question by means of a systematic deconstruction of lead-like inhibitors of the pVHL:HIF-1α interaction into their component fragments. Using biophys. techniques commonly employed for screening, we could only detect binding of fragments that violate the Rule of Three, are more complex than those typically screened against classical druggable targets, and occupy two adjacent binding subsites at the interface rather than just one. Analyses based on ligand and group lipophilicity efficiency of anchored fragments were applied to dissect the individual subsites and probe for binding hot spots. The implications of our findings for targeting protein interfaces by fragment-based approaches are discussed. In the experiment, the researchers used many compounds, for example, 3-Methylisoxazole-5-acetic Acid (cas: 19668-85-0Synthetic Route of C6H7NO3).
3-Methylisoxazole-5-acetic Acid (cas: 19668-85-0) belongs to isoxazole derivatives.Synthetically, isoxazoles serve as valuable precursors for the construction of diverse molecules, including many natural products. Fe(CO)5 efficiently cleaves the N–O bond of fused isoxazolo-1,4-quinones to give the corresponding imines.All the common reducing reagents failed to open the isoxazole ring.Synthetic Route of C6H7NO3
Referemce:
Isoxazole – Wikipedia,
Isoxazole | C3H3NO – PubChem