177358-18-8Relevant academic research and scientific papers
Chemoenzymatic Synthesis of a Library of Human Milk Oligosaccharides
Xiao, Zhongying,Guo, Yuxi,Liu, Yunpeng,Li, Lei,Zhang, Qing,Wen, Liuqing,Wang, Xuan,Kondengaden, Shukkoor Muhammed,Wu, Zhigang,Zhou, Jun,Cao, Xuefeng,Li, Xu,Ma, Cheng,Wang, Peng George
, p. 5851 - 5865 (2016/07/23)
Human milk oligosaccharides (HMOs) are a family of diverse unconjugated glycans that exist in human milk as one of the major components. Characterization, quantification, and biofunctional studies of HMOs remain a great challenge due to their diversity and complexity. The accessibility of a homogeneous HMO library is essential to solve these issues which have beset academia for several decades. In this study, an efficient chemoenzymatic strategy, namely core synthesis/enzymatic extension (CSEE), for rapid production of diverse HMOs was reported. On the basis of 3 versatile building blocks, 3 core structures were chemically synthesized via consistent use of oligosaccharyl thioether and oligosaccharyl bromide as glycosylation donors in a convergent fragment coupling strategy. Each of these core structures was then extended to up to 11 HMOs by 4 robust glycosyltransferases. A library of 31 HMOs were chemoenzymatically synthesized and characterized by MS and NMR. CSEE indeed provides a practical approach to harvest structurally defined HMOs for various applications.
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.
Synthesis of a D,D- and L,D-heptose-containing hexasaccharide corresponding to a structure from Haemophilus ducreyi lipopolysaccharides
Bernlind, Christian,Bennett, Simon,Oscarson, Stefan
, p. 481 - 492 (2007/10/03)
The synthesis of a linear hexasaccharide, 2-(4-trifluoroacetamidophenyl)ethyl (β-D-galactopyranosyl)-(1→4)-(2-acetamido-2-deoxy-β-D-glucopyranosyl)-(1→3)-(β-D-galactopyranosyl)-(1→4)-(D-glycero-α-D-manno-heptopyranosyl)-(1→6)-(β-D-glucopyranosyl)-(1→4)-L-
Synthesis of the Sda determinant and two analogous tetrasaccharides.
van Seeventer,Kamerling,Vliegenthart
, p. 181 - 195 (2007/10/03)
To contribute to the possibility of studying in greater detail the biological significance of Sda-containing glycans as occur in Tamm-Horsfall glycoprotein, the following three spacer-linked tetrasaccharides have been synthesized: the Sda determinant alpha-Neu p5Ac-(2-->3)-[beta- D-GalpNAc-(1-->4)]-beta-D-Galp-(1-->4)-beta-D-GlcpNAc-(1-->O)(CH2)5NH 2 (1), the Gal-analogue alpha-Neup5Ac-(2-->3)-[beta-D-Galp-(1-->4)]-beta-D-Galp-(1-->4) -beta-D-GlcpNAc-(1-->O)(CH2)5NH2 (2), and the GlcNAc-analogue alpha-Neup5Ac-(2-->3)-[beta-D-GlcpNAc-(1-->4)]- beta-D-Galp-(1-->4)-beta-D-GlcpNAc-(1-->O)(CH2)5NH2 (3). The general trisaccharide acceptor 5-azidopentyl (methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy- D-glycero-alpha-D-galactonon-2-ulopyranosylonate)-(2-->3)-(2 ,6-di-O-benzyl- beta-D-galactopyranosyl)-(1-->4)-3,6-di-O- benzyl-2-deoxy-2-phthalimido-beta-D-glucopyranoside was prepared, using methyl (phenyl 5- acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-2-thio-D-glycero-D-galacto- non- 2-ulopyranosid)- onate as the sialyl donor. For the syntheses of 1, 2, and 3 the glycosyl donors 3,4,6-tri-O- acetyl-2-deoxy-2-phthalimido-alpha-D-galactopyranosyl bromide, 2,3,4,6-tetra-O-acetyl-alpha-D- galactopyranosyl bromide, and 3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido -beta-D-glucopyranosyl trichloroacetimidate, respectively, proved to be the most suitable.
Synthesis of a hexasaccharide corresponding to a porcine zona pellucida fragment that inhibits porcine sperm-oocyte interaction in vitro
Spijker, Nynke M.,Keuning, Cor A.,Hooglugt, Mariska,Veeneman, Gerrit H.,Van Boeckel, Constant A. A.
, p. 5945 - 5960 (2007/10/03)
The synthesis of hexasaccharide 1, [galβ(1-4)GlcNAc[6OSO3]β(1-3)Galβ(1-4)GlcNAcβ(1-3)Galβ(1-3)GalNA cα-O(CH2)3NH2], which corresponds to a porcine zona pellucida fragment that inhibits porcine sperm-oocyte interaction, is described. Compound 1 was obtained from fully protected hexasaccharide 2, which was in turn constructed from protected Galβ(1-3)GalNAc disaccharide 5, containing an α-linked 3-azidopropyl spacer, and from lactosamine derivatives 3 and 4. Disaccharide 3 and 4 were prepared by coupling of selenophenyl glycoside 6 with glycosyl acceptors containing anomeric thioethyl groups. NIS/TfOH promoted coupling of disaccharide 4 with 5 afforded 29, which was transformed into the tetrasaccharide acceptor 30 by selective removal of the levulinoyl group. Glycosylation of 30 with 3 afforded protected hexasaccharide 2. Removal of the phthalimido groups, acetylation, followed by selective removal of the allyl group and sulphation, and finally complete deprotection afforded hexasaccharide 1.
