Source:http://linkedlifedata.com/resource/pubmed/id/15680592
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
2005-1-31
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pubmed:abstractText |
2,4-Dinitrophenyl 2-acetamido-2-deoxy-beta-d-glucopyranosyl-(1-->4)-2-deoxy-2-fluoro-beta-d-glucopyranoside (GN2FG-DNP) and 2-acetamido-2-deoxy-beta-d-glucopyranosyl-(1-->4)-2-deoxy-2-fluoro-beta-d-glucopyranosyl fluoride (GN2FG-F) were prepared using a divergent synthetic approach involving 10 steps. The key steps involved the preparation of 1-O-acetyl-3,6-di-O-benzyl-2-deoxy-2-fluoro-alpha/beta-d-glucopyranose using Selectfluor(trade mark) in the presence of acetic acid and the subsequent glycosylation of this acceptor to generate the core 2-fluorodisaccharide. After further elaboration, the target molecules were obtained and tested as probes of the mechanism of hen egg white lysozyme (HEWL). Compound GN2FG-DNP is not a substrate for the enzyme while compound GN2FG-F is cleaved slowly with an apparent K(m) greater than 5mM and a second-order rate constant of k(cat)/K(m)=9.6s(-1)M(-1). Comparison of this value to that estimated for the hydrolysis of beta-chitobiosyl fluoride by HEWL (1200s(-1)M(-1)) [Ballardie, F. W.; Capon, B.; Cuthbert, M. W.; Dearie, W. M. Bioorg. Chem.1977, 6, 483-509] revealed a 126-fold rate decrease upon substitution of a fluorine group for the 2-acetamido group of beta-chitobiosyl fluoride. This decrease resulted in the steady-state accumulation of an intermediate as visualized by mass spectrometry and the ultimate crystallographic determination of its structure [Vocadlo, D. J.; Davies, G. J.; Laine, R.; Withers, S. G. Nature2001, 412, 835-838].
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/2,4-Dinitrophenol,
http://linkedlifedata.com/resource/pubmed/chemical/Cellobiose,
http://linkedlifedata.com/resource/pubmed/chemical/Disaccharidases,
http://linkedlifedata.com/resource/pubmed/chemical/Molecular Probes,
http://linkedlifedata.com/resource/pubmed/chemical/Muramidase,
http://linkedlifedata.com/resource/pubmed/chemical/hen egg lysozyme
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0008-6215
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
28
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pubmed:volume |
340
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
379-88
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:15680592-2,4-Dinitrophenol,
pubmed-meshheading:15680592-Animals,
pubmed-meshheading:15680592-Catalysis,
pubmed-meshheading:15680592-Cellobiose,
pubmed-meshheading:15680592-Disaccharidases,
pubmed-meshheading:15680592-Molecular Probes,
pubmed-meshheading:15680592-Muramidase,
pubmed-meshheading:15680592-Substrate Specificity
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pubmed:year |
2005
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pubmed:articleTitle |
The chemical synthesis of 2-deoxy-2-fluorodisaccharide probes of the hen egg white lysozyme mechanism.
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pubmed:affiliation |
Department of Chemistry, University of British Columbia, Vancouver, BC, Canada V6T 1Z1.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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