| Synthesis of a glucuronic acid and glucose conjugate library and evaluation of effects on endothelial cell growth. | |
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MedLine Citation:
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PMID: 15261580 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Compounds that alter endothelial cell growth are of interest in the development of angiogenesis modulators. A structurally diverse series of saccharide derivatives (glycosylamide conjugates) have been synthesized and evaluated for their effects on bovine aortic endothelial cell (BAEC) growth. Heparin-albumin (HA) reduced BAEC growth by 32% at 10 microg/mL and a number of the novel saccharide conjugates from the library were found to mimic the effect of HA as they also inhibit endothelial cell survival under identical conditions. Two thiophene conjugates, thioglucamide (24% inhibition at 35 microM) and a related glucuronide (26% inhibition at 33 microM) were the most potent inhibitors of BAEC growth, as determined using a methylthiazol tetrazolium (MTT) assay. The effects of thioglucamide and HA on absolute cell number were also studied using cell counting experiments; thioglucamide (47% after 24 h) was more potent than indicated by the MTT assay and initially reduced the BAEC number to a greater extent than HA (30% after 24 h); however, its actions were over more rapidly than were HA's as cell growth had returned to levels of the control after 72 h where HA still caused 25% inhibition. The binding of the monosaccharide conjugates to fibroblast growth factor (FGF-2) in competition with heparin-albumin by ELISA was investigated to establish the possible mechanism by which glycoconjugates could alter growth but there was no general correlation between reduction in viable cell population and binding to FGF-2. No glycoconjugate reduced the proliferation of mouse mammary epithelial cells, nor did any alter gross cell morphology, supporting a proposal that the reduction in BAEC survival by monosaccharide conjugates such as thioglucamide is a result of the inhibition of cell proliferation rather than being an induction of cytotoxicity. These studies indicate that cell biological studies to determine the mechanism of action of the simple monosaccharide conjugates may be worthwhile. |
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Authors:
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Nigel Pitt; Rhona M Duane; Alan O'Brien; Helena Bradley; Stephen J Wilson; Kathy M O'Boyle; Paul V Murphy |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Carbohydrate research Volume: 339 ISSN: 0008-6215 ISO Abbreviation: Carbohydr. Res. Publication Date: 2004 Aug |
Date Detail:
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Created Date: 2004-07-20 Completed Date: 2005-08-05 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0043535 Medline TA: Carbohydr Res Country: Netherlands |
Other Details:
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Languages: eng Pagination: 1873-87 Citation Subset: IM |
Affiliation:
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Centre for Synthesis and Chemical Biology, Department of Chemistry, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Carbohydrate Conformation Carbohydrate Sequence Cattle Cell Division / drug effects Cell Line Combinatorial Chemistry Techniques Endothelial Cells / drug effects*, metabolism Fibroblast Growth Factor 2 / pharmacology Glucose / chemistry* Glucosides / pharmacology Glucuronic Acid / chemical synthesis*, chemistry, pharmacology* Heparin / pharmacology Mice Molecular Sequence Data Molecular Structure Oligosaccharides / chemical synthesis*, chemistry, pharmacology* Serum Albumin / pharmacology Structure-Activity Relationship Thiophenes / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Glucosides; 0/Oligosaccharides; 0/Serum Albumin; 0/Thiophenes; 0/thioglucamide; 103107-01-3/Fibroblast Growth Factor 2; 50-99-7/Glucose; 576-37-4/Glucuronic Acid; 9005-49-6/Heparin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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