Amino Acids Bearing Aromatic or Heteroaromatic Substituents as a New Class of Ligands for the Lysosomal Sialic Acid Transporter Sialin was written by Dubois, Lilian;Pietrancosta, Nicolas;Cabaye, Alexandre;Fanget, Isabelle;Debacker, Cecile;Gilormini, Pierre-Andre;Dansette, Patrick M.;Dairou, Julien;Biot, Christophe;Froissart, Roseline;Goupil-Lamy, Anne;Bertrand, Hugues-Olivier;Acher, Francine C.;McCort-Tranchepain, Isabelle;Gasnier, Bruno;Anne, Christine. And the article was included in Journal of Medicinal Chemistry in 2020.Application of 638-07-3 The following contents are mentioned in the article:
Sialin, encoded by the SLC17A5 gene, is a lysosomal sialic acid transporter defective in Salla disease, a rare inherited leukodystrophy. It also enables metabolic incorporation of exogenous sialic acids, leading to autoantibodies against N-glycolylneuraminic acid in humans. Here, we identified a novel class of human sialin ligands by virtual screening and structure-activity relationship studies. The ligand scaffold is characterized by an amino acid backbone with a free carboxylate, an N-linked aromatic or heteroaromatic substituent, and a hydrophobic side chain. The most potent compound, 45 (LSP12-3129), inhibited N-acetylneuraminic acid 1 (Neu5Ac) transport in a non-competitive manner with IC50 â?2.5μM, a value 400-fold lower than the KM for Neu5Ac. In vitro and mol. docking studies attributed the non-competitive character to selective inhibitor binding to the Neu5Ac site in a cytosol-facing conformation. Moreover, compound 45 rescued the trafficking defect of the pathogenic mutant (R39C) causing Salla disease. This new class of cell-permeant inhibitors provides tools to investigate the physiol. roles of sialin and help develop pharmacol. chaperones for Salla disease. This study involved multiple reactions and reactants, such as Ethyl 4-chloro-3-oxobutanoate (cas: 638-07-3Application of 638-07-3).
Ethyl 4-chloro-3-oxobutanoate (cas: 638-07-3) belongs to organic chlorides. Organic chlorides are compounds containing a carbon-chlorine bond, which are widely used in the oil field as a wax dissolver. The haloform reaction, using chlorine and sodium hydroxide, is also able to generate alkyl halides from methyl ketones, and related compounds. Chloroform was formerly produced thus.Application of 638-07-3
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Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics