53298-33-2Relevant articles and documents
Amino Acids Bearing Aromatic or Heteroaromatic Substituents as a New Class of Ligands for the Lysosomal Sialic Acid Transporter Sialin
Dubois, Lilian,Pietrancosta, Nicolas,Cabaye, Alexandre,Fanget, Isabelle,Debacker, Cécile,Gilormini, Pierre-André,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
supporting information, p. 8231 - 8249 (2020/09/21)
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 ≈ 2.5 μM, a value 400-fold lower than the KM for Neu5Ac. In vitro and molecular 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 physiological roles of sialin and help develop pharmacological chaperones for Salla disease.
9-Fluorenylmethyl Pentafluorophenyl Carbonate as a Useful Reagent for the Preparation of N-9-Fluorenylmethyloxycarbonylamino Acids and their Pentafluorophenyl Esters
Schoen, Istvan,Kisfaludy, Lajos
, p. 303 - 305 (2007/10/02)
9-Fluorenylmethyl pentafluorophenyl carbonate is a useful reagent for the efficient, side reaction-free introduction of N-9-fluorenylmethyloxycarbonyl protecting group into amino acids and for the subsequent preparation of their pentafluorophenyl esters.Some new compounds of both types are described.