A chemoenzymatic synthesis of UDP-(2-deoxy-2-fluoro)galactose and evaluation of its interaction with galactosyltransferase

Hayashi, Takashi; Murray, Brion W.; Wang, Ruo; Wong, Chi‐Huey

doi:10.1016/s0968-0896(96)00263-5

Cited by 49 publications

(25 citation statements)

References 30 publications

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“…2.7.7.12; Sigma; ref. 18), after which the product was reacted with sulfosuccinimidyl-6-(biotinamido)hexanoate (sulfo-NHS-LC-biotin; Pierce). The resulting product, uridine-5 ¶-diphospho N-(6-biotinamidohexanoyl)-(2-amino-2-deoxy)-D-galactosamine (UDP-GalN-biotin), was chromatographically purified to homogeneity and characterized by MALDI-TOF mass spectrometry and 1 H nuclear magnetic resonance spectroscopy (NMR).…”

Section: Methodsmentioning

confidence: 99%

Analysis of the Human Cancer Glycome Identifies a Novel Group of Tumor-AssociatedN-Acetylglucosamine Glycan Antigens

et al. 2009

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The cell surface is covered by a dense layer of protein-and lipid-linked glycans. Although it has been known that distinct glycan structures are associated with cancer, the whole spectrum of cancer-associated glycans has remained undiscovered. In the present study, we analyzed the protein-linked cancer glycome by matrix-assisted laser desorption/ionization time-of-flight mass spectrometric glycan profiling of cancer patient tissue samples. In lung cancer, we detected accumulation of a novel group of tumor-associated glycans. These protein-linked glycans carried abnormal nonreducing terminal B-N-acetyl-D-glucosamine (GlcNAc) residues. A similar phenomenon was also detected in structural analyses of tumor-derived glycosphingolipids. This showed that glycan biosynthesis may dramatically change in cancer and that direct glycome analysis can detect the resulting marker glycans. Based on the structural knowledge, we further devised a covalent labeling technique for the detection of GlcNAcexpressing tumors with a specific transferase enzyme. In normal tissues, terminal GlcNAc antigens are capped by galactosylation. Similarly to common cancer-associated glycan antigens T, Tn, and sialyl-Tn, the newly discovered GlcNAc antigens result from incomplete glycosylation. In conclusion, the identified terminal GlcNAc glycans should be recognized as a novel class of tumor markers. [Cancer Res 2009;69(14):5811-9]

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Section: Methodsmentioning

confidence: 99%

Analysis of the Human Cancer Glycome Identifies a Novel Group of Tumor-AssociatedN-Acetylglucosamine Glycan Antigens

et al. 2009

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“…Secondary deuterium isotope effects observed with [1-2 H]-UDP-galactose (Kim et al, 1988) and competitive inhibition by UDP-(2-deoxy-2-fluoro)-galactose (Hayashi et al, 1997) indicate that the galactose transfer reaction mechanism involves an intermediate in which the anomeric C of galactose has sp2 character and the UDP to galactose bond is substantially cleaved in the transition state. The stabilization of a cationic galactose moiety by this anionic region of β4GT-1 in the transition state provides a plausible, but not unique, explanation of the results reported here.…”

Section: Discussionmentioning

confidence: 99%

Role of a conserved acidic cluster in bovine 1,4 galactosyltransferase-1 probed by mutagenesis of a bacterially expressed recombinant enzyme

et al. 1999

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The truncated catalytic domain of bovine β1,4 galactosyltransferase-1 was expressed as inclusion bodies in E.coli and folded to generate 10-15 mg of active enzyme per liter of bacterial culture after extraction and purification under denaturing conditions. Mutations were introduced to investigate the roles of Trp312, Asp318, and Asp320, components of a highly conserved region of sequence in all known β4GT-1 homologues that includes a cluster of acidic residues. Near and far UV CD spectra of the mutants indicate that the substitutions did not perturb the secondary and tertiary structure of β4GT-1, and steady state kinetic studies indicate only minor effects on the response to an essential metal cofactor. However substitutions for the two aspartyl residues result in a reduction in catalytic efficiency of a magnitude that suggests they are important for catalysis. It seems possible that this anionic center may act in stabilizing a carbocation formed from the galactose component of the donor substrate in the transition state, reflecting a common reaction mechanism for β-galactosyltransferase reactions.

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“…Various representatives of β-lactam antibiotics 164 were synthesized by intramolecular cyclization of an azide group and a triple bond [7,94]. In connection with the fact that various imino sugars are important inhibitors of glycosidases and glycosyltransferases [95] a method was recently developed for the synthesis of new bicyclic triazoles 165 starting from transformed natural sugars [96]. When treated with sodium azide in DMF the tosylates and mesylates of D-arabinose and L-fucose 166, produced in several stages, undergo cyclization in situ to the triazoline intermediate 167.…”

Section: Intramolecular Cycloaddition Of Azides At Multiple Bondsmentioning

confidence: 99%

Condensed 1,2,3-triazoles (review)

Shafran¹,

Бакулев²,

Rozin³

et al. 2008

Chem Heterocycl Comp

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A chemoenzymatic synthesis of UDP-(2-deoxy-2-fluoro)galactose and evaluation of its interaction with galactosyltransferase

Cited by 49 publications

References 30 publications

Analysis of the Human Cancer Glycome Identifies a Novel Group of Tumor-AssociatedN-Acetylglucosamine Glycan Antigens

Analysis of the Human Cancer Glycome Identifies a Novel Group of Tumor-AssociatedN-Acetylglucosamine Glycan Antigens

Role of a conserved acidic cluster in bovine 1,4 galactosyltransferase-1 probed by mutagenesis of a bacterially expressed recombinant enzyme

Condensed 1,2,3-triazoles (review)

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