Synthetic Site-Selectively Mono-6-O-Sulfated Heparan Sulfate Dodecasaccharide Shows Anti-Angiogenic Properties In Vitro and Sensitizes Tumors to Cisplatin In Vivo

Egle Avizienyte; Claire L. Cole; Graham Rushton; Gavin J. Miller; Antonella Bugatti; Marco Presta; John M. Gardiner; Gordon C. Jayson

doi:10.1371/journal.pone.0159739

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Research Article

Synthetic Site-Selectively Mono-6-O-Sulfated Heparan Sulfate Dodecasaccharide Shows Anti-Angiogenic Properties In Vitro and Sensitizes Tumors to Cisplatin In Vivo

Egle Avizienyte ,

* E-mail: egle.avizienyte@ics.manchester.ac.uk (EA); gordon.jayson@ics.manchester.ac.uk (GCJ)

Affiliation Institute of Cancer Sciences, Faculty of Medical and Human Sciences, The University of Manchester, Manchester M20 4BX, United Kingdom
⨯
Claire L. Cole,

Affiliation Institute of Cancer Sciences, Faculty of Medical and Human Sciences, The University of Manchester, Manchester M20 4BX, United Kingdom
⨯
Graham Rushton,

Affiliation Institute of Cancer Sciences, Faculty of Medical and Human Sciences, The University of Manchester, Manchester M20 4BX, United Kingdom
⨯
Gavin J. Miller,

Current address: Synthesis & Medicinal Chemistry Cluster, Keele University, Keele, Staffordshire, ST5 5BG, UK

Affiliation School of Chemistry and Manchester Interdisciplinary Biocentre, The University of Manchester, Manchester M1 7ND, United Kingdom
⨯
Antonella Bugatti,

Affiliation Unit of General Pathology and Immunology, Department of Biomedical Sciences and Biotechnology, University of Brescia, Viale Europa 11, 25123 Brescia, Italy
⨯
Marco Presta,

Affiliation Unit of General Pathology and Immunology, Department of Biomedical Sciences and Biotechnology, University of Brescia, Viale Europa 11, 25123 Brescia, Italy
⨯
John M. Gardiner,

Affiliation School of Chemistry and Manchester Interdisciplinary Biocentre, The University of Manchester, Manchester M1 7ND, United Kingdom
⨯
Gordon C. Jayson

* E-mail: egle.avizienyte@ics.manchester.ac.uk (EA); gordon.jayson@ics.manchester.ac.uk (GCJ)

Affiliation Institute of Cancer Sciences, Faculty of Medical and Human Sciences, The University of Manchester, Manchester M20 4BX, United Kingdom
⨯

Synthetic Site-Selectively Mono-6-O-Sulfated Heparan Sulfate Dodecasaccharide Shows Anti-Angiogenic Properties In Vitro and Sensitizes Tumors to Cisplatin In Vivo

Egle Avizienyte,
Claire L. Cole,
Graham Rushton,
Gavin J. Miller,
Antonella Bugatti,
Marco Presta,
John M. Gardiner,
Gordon C. Jayson

Published: August 4, 2016
https://doi.org/10.1371/journal.pone.0159739

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Chemical synthesis is a superior tool to explore the biology of heparin sulphation patterns.

Posted by SteenUldall on 11 Aug 2016 at 09:29 GMT

When I did all of the synthesis of the Mono6S dodecasaccharide I had not imagined how much impact one sulfate group could have on the biology of these molecules. It was really hard work making these compounds on gram scale. I remember coming back early from my Christmas holiday 27th of December and working on New years eve to meet the milestone of delivering the mono6S dodecasaccharide in January on gram scale. So it is gratifying to see the biological studies that have been made possible by all my hard work.

Only chemical synthesis makes it possible to design and explore unusual heparin sulphation patterns on material of the highest purity. And as such I believe this paper is an important step towards identifying new medicinal targets that could be only made by chemical synthesis.

Competing interests declared: I worked on this project.

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Synthetic Site-Selectively Mono-6-O-Sulfated Heparan Sulfate Dodecasaccharide Shows Anti-Angiogenic Properties In Vitro and Sensitizes Tumors to Cisplatin In Vivo

Synthetic Site-Selectively Mono-6-O-Sulfated Heparan Sulfate Dodecasaccharide Shows Anti-Angiogenic Properties In Vitro and Sensitizes Tumors to Cisplatin In Vivo

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Chemical synthesis is a superior tool to explore the biology of heparin sulphation patterns.

Posted by SteenUldall on 11 Aug 2016 at 09:29 GMT