Efficient chemical synthesis of heparin-like octa-, deca- and dodecasaccharides and inhibition of FGF2- and VEGF165-mediated endothelial cell functions

Gavin J. Miller; Steen U. Hansen; Egle Avizienyte; Graham Rushton; Claire Cole; Gordon C. Jayson; John M. Gardiner

doi:10.1039/C3SC51217G

Efficient chemical synthesis of heparin-like octa-, deca- and dodecasaccharides and inhibition of FGF2- and VEGF₁₆₅-mediated endothelial cell functions

Gavin J. Miller,^a Steen U. Hansen,^a Egle Avizienyte,^b Graham Rushton,^b Claire Cole,^b Gordon C. Jayson^b and John M. Gardiner*^a

Author affiliations

* Corresponding authors

^a Manchester Institute of Biotechnology, School of Chemistry, Faculty of Engineering and Physical Sciences, The University of Manchester, 131 Princess Street, Manchester M1 7DN, UK
E-mail: gardiner@manchester.ac.uk
Tel: +44 (0)161 306 4530

^b School of Cancer and Enabling Sciences, University of Manchester, UK
E-mail: Gordon.Jayson2@christie.nhs.uk
Fax: +44 (0)161 446 8565
Tel: +44 (0)161 446 3740

Abstract

A concise chemical synthesis of a series of structurally-defined heparin-like oligosaccharides is described. This work provides an efficient entry to octa-, deca-, and dodecasaccharides, including the first synthesis of (GlcNS6S-IdoA2S)₅ and (GlcNS6S-IdoA2S)₆. Evaluation of the in vitro activity of these species against FGF2- and VEGF₁₆₅-dependent endothelial cell proliferation and migration establishes that octa- and decasaccharides are more potent in targeting FGF2-induced effects, where cell migration is affected more significantly than proliferation. These structure–activity relationships exemplify the significance of 6-O-sulfation in regulating the activity of angiogenic growth factors.

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Publication details

The article was received on 03 May 2013, accepted on 26 May 2013 and first published on 28 May 2013

Article type: Edge Article

DOI: 10.1039/C3SC51217G

Citation: Chem. Sci., 2013,4, 3218-3222

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Efficient chemical synthesis of heparin-like octa-, deca- and dodecasaccharides and inhibition of FGF2- and VEGF₁₆₅-mediated endothelial cell functions

G. J. Miller, S. U. Hansen, E. Avizienyte, G. Rushton, C. Cole, G. C. Jayson and J. M. Gardiner, Chem. Sci., 2013, 4, 3218
DOI: 10.1039/C3SC51217G
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Chemical Science

Efficient chemical synthesis of heparin-like octa-, deca- and dodecasaccharides and inhibition of FGF2- and VEGF₁₆₅-mediated endothelial cell functions

Abstract

Supplementary files

Publication details

Efficient chemical synthesis of heparin-like octa-, deca- and dodecasaccharides and inhibition of FGF2- and VEGF₁₆₅-mediated endothelial cell functions

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