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# Organic Chemistry # Trifluoromethylation of Alkyl Radicals in Aqueous SolutionJ. Am. Chem. Soc. Abstract: The copper-mediated trifluoromethylation of alkyl radicals is described. The combination of Et3SiH and K2S2O8 initiates the radical reactions of alkyl bromides or iodides with BPyCu(CF3)3 (BPy = 2,2’-bipyridine) in aqueous acetone at room temperature to afford the corresponding trifluoromethylation products in good yield. The protocol is applicable to various primary and secondary alkyl halides and exhibits wide functional group compatibility. A mechanism involving trifluoromethyl group transfer from Cu(II)–CF3 intermediates to alkyl radicals is proposed. Link to CBG： http://www./news/art?id=4661 Link to the article： http://pubs./doi/10.1021/jacs.7b06044 # Medicinal Chemistry # Discovery of a covalent kinase inhibitor from a DNA-encoded small-molecule library X protein library selection J. Am. Chem. Soc. Abstract:We previously reported interaction determination using unpurified proteins (IDUP), a method to selectively amplify DNA sequences encoding ligand:target pairs from a mixture of DNA-linked small molecules and unpurified protein targets in cell lysates. In this study we applied IDUP to libraries of DNA-encoded bioactive compounds and DNA-tagged human kinases to identify ligand:protein binding partners out of 32,096 possible combinations in a single solution-phase library × library experiment. The results recapitulated known small molecule:protein interactions and also revealed that ethacrynic acid is a novel ligand and inhibitor of MAP2K6 kinase. Ethacrynic acid inhibits MAP2K6 in part through alkylation of a non-conserved cysteine residue. This work validates the ability of IDUP to discover ligands for proteins of biomedical relevance. Link to CBG： http://www./news/art?id=4660 Link to the article： http://pubs./doi/10.1021/jacs.7b04880 # Biological Chemistry # An Assay Based on SAMDI Mass Spectrometry for Profiling Protein Interaction DomainsJ. Am. Chem. Soc. Abstract: This paper describes an assay that can profile the binding of a protein to ligands, and can rank the affinities of a library of ligands. The method is based on the enhanced rate of an enzyme-mediated reaction that follows from colocalization of the enzyme and substrate by a protein-ligand interaction. This assay uses a self-assembled monolayer that presents a candidate peptide ligand for a receptor and a peptide substrate for an enzyme. The receptor is prepared as a fusion to the relevant enzyme so that binding of the receptor the immobilized ligand brings the enzyme to the surface where it can more rapidly modify its substrate. The extent of conversion of the substrate to product is therefore a measure of the average time the ligand-receptor complex is present, and is quantified using the SAMDI mass spectrometry technique. The approach is used to profile the binding of chromodomain proteins to methylated lysine peptides derived from the histone 3 protein. The relative affinities for the peptide ligands found in this work agreed with results from prior studies. Additionally, this work revealed cross-talk interactions whereby phosphorylation of certain residues impaired binding of chromodomains to the peptide ligands. The method presented here, which we term Protein Interaction by SAMDI (PI-SAMDI), has the advantages that it is applicable to low affinity interactions because the complexes are not observed directly, but rather leave a ‘covalent record’ of the interaction that is measured with mass spectrometry and because it is compatible with laboratory automation for high throughput analysis. Link to CBG： http://www./news/art?id=4658 Link to the article： http://pubs./doi/10.1021/jacs.7b03805 了解更多最全、最新論文快訊 登錄CBG官網(wǎng)（www.） 下載ChemBeanGo APP CBG資訊 ∣知識(shí)就是力量 |
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