97242-79-0Relevant articles and documents
Selectively Deoxyfluorinated N-Acetyllactosamine Analogues as 19F NMR Probes to Study Carbohydrate-Galectin Interactions
Kurfi?t, Martin,Dra?ínsky, Martin,?ervenková ??astná, Lucie,Cu?ínová, Petra,Hamala, Vojtěch,Hovorková, Michaela,Bojarová, Pavla,Karban, Jind?ich
, p. 13040 - 13051 (2021/08/07)
Galectins are widely expressed galactose-binding lectins implied, for example, in immune regulation, metastatic spreading, and pathogen recognition. N-Acetyllactosamine (Galβ1-4GlcNAc, LacNAc) and its oligomeric or glycosylated forms are natural ligands of galectins. To probe substrate specificity and binding mode of galectins, we synthesized a complete series of six mono-deoxyfluorinated analogues of LacNAc, in which each hydroxyl has been selectively replaced by fluorine while the anomeric position has been protected as methyl β-glycoside. Initial evaluation of their binding to human galectin-1 and -3 by ELISA and 19F NMR T2-filter revealed that deoxyfluorination at C3, C4′ and C6′ completely abolished binding to galectin-1 but very weak binding to galectin-3 was still detectable. Moreover, deoxyfluorination of C2′ caused an approximately 8-fold increase in the binding affinity towards galectin-1, whereas binding to galectin-3 was essentially not affected. Lipophilicity measurement revealed that deoxyfluorination at the Gal moiety affects log P very differently compared to deoxyfluorination at the GlcNAc moiety.
Combining weak affinity chromatography, NMR spectroscopy and molecular simulations in carbohydrate-lysozyme interaction studies
Landstroem, Jens,Bergstroem, Maria,Hamark, Christoffer,Ohlson, Sten,Widmalm, Goeran
, p. 3019 - 3032 (2012/05/07)
By examining the interactions between the protein hen egg-white lysozyme (HEWL) and commercially available and chemically synthesized carbohydrate ligands using a combination of weak affinity chromatography (WAC), NMR spectroscopy and molecular simulations, we report on new affinity data as well as a detailed binding model for the HEWL protein. The equilibrium dissociation constants of the ligands were obtained by WAC but also by NMR spectroscopy, which agreed well. The structures of two HEWL-disaccharide complexes in solution were deduced by NMR spectroscopy using 1H saturation transfer difference (STD) effects and transferred 1H,1H-NOESY experiments, relaxation-matrix calculations, molecular docking and molecular dynamics simulations. In solution the two disaccharides β-d-Galp-(1→4) -β-d-GlcpNAc-OMe and β-d-GlcpNAc-(1→4)-β-d-GlcpNAc-OMe bind to the B and C sites of HEWL in a syn-conformation at the glycosidic linkage between the two sugar residues. Intermolecular hydrogen bonding and CH/π-interactions form the basis of the protein-ligand complexes in a way characteristic of carbohydrate-protein interactions. Molecular dynamics simulations with explicit water molecules of both the apo-form of the protein and a ligand-protein complex showed structural change compared to a crystal structure of the protein. The flexibility of HEWL as indicated by a residue-based root-mean-square deviation analysis indicated similarities overall, with some residue specific differences, inter alia, for Arg61 that is situated prior to a flexible loop. The Arg61 flexibility was notably larger in the ligand-complexed form of HEWL. N,N′-Diacetylchitobiose has previously been observed to bind to HEWL at the B and C sites in water solution based on 1H NMR chemical shift changes in the protein whereas the disaccharide binds at either the B and C sites or the C and D sites in different crystal complexes. The present study thus highlights that protein-ligand complexes may vary notably between the solution and solid states, underscoring the importance of targeting the pertinent binding site(s) for inhibition of protein activity and the advantages of combining different techniques in a screening process. The Royal Society of Chemistry 2012.
Efficient Synthesis of 3,6-Dideoxy-β-D-arabino-hexopyranosyl-Terminated LacdiNac Glycan Chains of the Trichinella spiralis Parasite
Nitz, Mark,Bundle, David R.
, p. 3064 - 3073 (2007/10/03)
The synthesis of a linear trisaccharide epitope of the Trichinella spiralis N-linked glycan, in a form amenable to glycoconjugate formation, is reported. The trisaccharide contains the synthetically challenging LacdiNAc [β-GalpNAc(1→4)-β-GlcpNAc] element,
Synthesis of a fucosylated and a non-fucosylated core structure of xylose-containing carbohydrate chains from N-glycoproteins
Van der Ven,Kerekgyarto,Kamerling,Liptak,Vliegenthart
, p. 45 - 62 (2007/10/02)
The synthesis is reported of methyl 2-acetamido-4-O-[2-acetamido-2-deoxy-4-O-(3,6-di-O-α-D-mannopyranosyl-2-O-β-D -xylopyranosyl-β-D-mannopyranosyl)-β- D-glucopyranosyl]-2-deoxy-β-D-glucopyranoside (4) and methyl 2-acetamido-4-O-[2-acetamido-2-deoxy-4-O-(
Preparation of disaccharides having a β-D-mannopyranosyl group from N-phthaloyllactosamine derivatives by double or triple SN2 substitution
Alais, Jocelyne,David, Serge
, p. 69 - 77 (2007/10/02)
Condensation of 1,2,3,4,6-penta-O-acetyl-β-D-galactopyranose with methyl 3,6-di-O-benzyl-2-deoxy-2-phthalimido-β-D-glucopyranoside, followed by alkaline methanolysis, gave a derivative of lactosamine that has an unsubstituted β-D-galactopyranosyl group.Tr
