Mechanisms of heparanase inhibition by the heparan sulfate mimetic PG545 and three structural analogues()

The tetrasaccharide heparan sulfate (HS) mimetic PG545, a clinical anti-cancer candidate, is an inhibitor of the HS-degrading enzyme heparanase. The kinetics of heparanase inhibition by PG545 and three structural analogues were investigated to understand their modes of inhibition. The cholestanol ag...

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Autores principales: Hammond, Edward, Handley, Paul, Dredge, Keith, Bytheway, Ian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2013
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3821029/
https://www.ncbi.nlm.nih.gov/pubmed/24251094
http://dx.doi.org/10.1016/j.fob.2013.07.007
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author Hammond, Edward
Handley, Paul
Dredge, Keith
Bytheway, Ian
author_facet Hammond, Edward
Handley, Paul
Dredge, Keith
Bytheway, Ian
author_sort Hammond, Edward
collection PubMed
description The tetrasaccharide heparan sulfate (HS) mimetic PG545, a clinical anti-cancer candidate, is an inhibitor of the HS-degrading enzyme heparanase. The kinetics of heparanase inhibition by PG545 and three structural analogues were investigated to understand their modes of inhibition. The cholestanol aglycon of PG545 significantly increased affinity for heparanase and also modified the inhibition mode. For the tetrasaccharides, competitive inhibition was modified to parabolic competition by the addition of the cholestanol aglycon. For the trisaccharides, partial competitive inhibition was modified to parabolic competition. A schematic model to explain these findings is presented.
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spelling pubmed-38210292013-11-18 Mechanisms of heparanase inhibition by the heparan sulfate mimetic PG545 and three structural analogues() Hammond, Edward Handley, Paul Dredge, Keith Bytheway, Ian FEBS Open Bio Article The tetrasaccharide heparan sulfate (HS) mimetic PG545, a clinical anti-cancer candidate, is an inhibitor of the HS-degrading enzyme heparanase. The kinetics of heparanase inhibition by PG545 and three structural analogues were investigated to understand their modes of inhibition. The cholestanol aglycon of PG545 significantly increased affinity for heparanase and also modified the inhibition mode. For the tetrasaccharides, competitive inhibition was modified to parabolic competition by the addition of the cholestanol aglycon. For the trisaccharides, partial competitive inhibition was modified to parabolic competition. A schematic model to explain these findings is presented. Elsevier 2013-08-02 /pmc/articles/PMC3821029/ /pubmed/24251094 http://dx.doi.org/10.1016/j.fob.2013.07.007 Text en © 2013 The Authors http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-No Derivative Works License, which permits non-commercial use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Article
Hammond, Edward
Handley, Paul
Dredge, Keith
Bytheway, Ian
Mechanisms of heparanase inhibition by the heparan sulfate mimetic PG545 and three structural analogues()
title Mechanisms of heparanase inhibition by the heparan sulfate mimetic PG545 and three structural analogues()
title_full Mechanisms of heparanase inhibition by the heparan sulfate mimetic PG545 and three structural analogues()
title_fullStr Mechanisms of heparanase inhibition by the heparan sulfate mimetic PG545 and three structural analogues()
title_full_unstemmed Mechanisms of heparanase inhibition by the heparan sulfate mimetic PG545 and three structural analogues()
title_short Mechanisms of heparanase inhibition by the heparan sulfate mimetic PG545 and three structural analogues()
title_sort mechanisms of heparanase inhibition by the heparan sulfate mimetic pg545 and three structural analogues()
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3821029/
https://www.ncbi.nlm.nih.gov/pubmed/24251094
http://dx.doi.org/10.1016/j.fob.2013.07.007
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