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

Hammond, Edward, Handley, Paul, Dredge, Keith and Bytheway, Ian (2013) Mechanisms of heparanase inhibition by the heparan sulfate mimetic PG545 and three structural analogues. FEBS Open Bio, 3 346-351. doi:10.1016/j.fob.2013.07.007


Author Hammond, Edward
Handley, Paul
Dredge, Keith
Bytheway, Ian
Title Mechanisms of heparanase inhibition by the heparan sulfate mimetic PG545 and three structural analogues
Journal name FEBS Open Bio   Check publisher's open access policy
ISSN 2211-5463
Publication date 2013
Year available 2013
Sub-type Article (original research)
DOI 10.1016/j.fob.2013.07.007
Open Access Status DOI
Volume 3
Start page 346
End page 351
Total pages 6
Place of publication Amsterdam, The Netherlands
Publisher Elsevier BV
Collection year 2014
Language eng
Subject 1300 Biochemistry, Genetics and Molecular Biology
Abstract 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.
Keyword Cancer
Heparanase
Inhibitor
Kinetics
PG545
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
Centre for Integrated Preclinical Drug Development Publications
 
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Created: Thu, 28 Nov 2013, 19:03:01 EST by System User on behalf of Centre for Integrated Preclinical Drug Development