Design, synthesis, FGF-1 binding, and molecular modeling studies of conformationally flexible heparin mimetic disaccharides

Liu, Ligong, Bytheway, Ian, Karoli, Tomislav, Fairweather, Jon K., Cochran, Siska, Li, Caiping and Ferro, Vito (2008) Design, synthesis, FGF-1 binding, and molecular modeling studies of conformationally flexible heparin mimetic disaccharides. Bioorganic & Medicinal Chemistry Letters, 18 1: 344-349. doi:10.1016/j.bmcl.2007.10.071


Author Liu, Ligong
Bytheway, Ian
Karoli, Tomislav
Fairweather, Jon K.
Cochran, Siska
Li, Caiping
Ferro, Vito
Title Design, synthesis, FGF-1 binding, and molecular modeling studies of conformationally flexible heparin mimetic disaccharides
Journal name Bioorganic & Medicinal Chemistry Letters   Check publisher's open access policy
ISSN 1464-3405
0960-894X
Publication date 2008-01-01
Year available 2007
Sub-type Article (original research)
DOI 10.1016/j.bmcl.2007.10.071
Volume 18
Issue 1
Start page 344
End page 349
Total pages 6
Place of publication Oxford, U.K.
Publisher Pergamon
Language eng
Subject 0601 Biochemistry and Cell Biology
Abstract Disaccharide mimetics of a heparin sequence that binds to fibroblast growth factors were prepared by coupling a d-galactose donor with a methyl β-d-gluco- or xylopyranoside acceptor. When fully sulfated, the glucose or xylose moieties exist in solution in equilibrium between the 4C1 and 1C4 conformers, as confirmed by 1H NMR spectroscopy, thus mimicking the conformationally flexible l-iduronic acid found in heparin. Docking calculations showed that the predicted locations of disaccharide sulfo groups in the binding site of FGF-1 are consistent with the positions observed for co-crystallized heparin-derived oligosaccharides. Predicted binding affinities are in accord with experimental Kd values obtained from binding assays and are similar to the predicted values for a model heparin disaccharide. Copyright 2007 Elsevier Ltd.
Keyword Fibroblast growth factors
Disaccharides
Heparin mimetics
Q-Index Code C1
Q-Index Status Provisional Code
Additional Notes Available online 25 October 2007

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
Institute for Molecular Bioscience - Publications
 
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Created: Mon, 04 Jan 2010, 14:05:20 EST by Michael Affleck on behalf of Institute for Molecular Bioscience