Synthesis of a heparan sulfate mimetic library targeting FGF and VEGF via click chemistry on a monosaccharide template

Liu, Ligong, Li, Caiping, Cochran, Siska, Jimmink, Shane and Ferro, Vito (2012) Synthesis of a heparan sulfate mimetic library targeting FGF and VEGF via click chemistry on a monosaccharide template. ChemMedChem, 7 7: 1267-1275. doi:10.1002/cmdc.201200151

Attached Files (Some files may be inaccessible until you login with your UQ eSpace credentials)
Name Description MIMEType Size Downloads

Author Liu, Ligong
Li, Caiping
Cochran, Siska
Jimmink, Shane
Ferro, Vito
Total Author Count Override 5
Title Synthesis of a heparan sulfate mimetic library targeting FGF and VEGF via click chemistry on a monosaccharide template
Journal name ChemMedChem   Check publisher's open access policy
ISSN 1860-7179
1860-7187
Publication date 2012-07
Sub-type Article (original research)
DOI 10.1002/cmdc.201200151
Volume 7
Issue 7
Start page 1267
End page 1275
Total pages 10
Place of publication Weinheim, Germany
Publisher Wiley
Collection year 2013
Language eng
Formatted abstract
A disulfated methyl 6-azido-6-deoxy-α-D-mannopyranoside template was used as a core structure for binding to the angiogenic growth factors FGF-1, FGF-2, and VEGF. The core structure was diversified in a rapid, parallel manner by employing the CuI-catalyzed Huisgen azide–alkyne cycloaddition (“click”) reaction. The diversity was further extended by incorporating a Swern oxidation–Wittig reaction sequence on a click adduct of propargyl alcohol. Thus, the sulfated core was linked by various spacers to selected hydrophobic or polar motifs, which were designed to probe the protein surface surrounding the cationic heparan sulfate binding sites of the growth factors in order to improve affinity and selectivity. The affinities of the compounds for the growth factors were measured by surface plasmon resonance solution affinity assays. A lead compound was identified with micromolar binding affinity toward both FGF-1 and VEGF (Kd=84 and 49 μM, respectively) and good selectivity over FGF-2 (29- and 51-fold, respectively).
Keyword Click chemistry
Drug design
Fibroblast growth factors
Heparin mimetics
Vascular endothelial growth factor
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
School of Chemistry and Molecular Biosciences
Institute for Molecular Bioscience - Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 6 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 5 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Wed, 30 May 2012, 10:40:21 EST by Lucy O'Brien on behalf of Institute for Molecular Bioscience