Structural and conformational studies of the heparan sulfate mimetic PI-88

No Thumbnail Available
File version
Author(s)
Elli, Stefano
Stancanelli, Eduardo
Handley, Paul N
Carroll, Anthony
Urso, Elena
Guerrini, Marco
Ferro, Vito
Griffith University Author(s)
Primary Supervisor
Other Supervisors
Editor(s)
Date
2018
Size
File type(s)
Location
License
Abstract

The heparan sulfate mimetic PI-88 is a complex mixture of sulfated oligosaccharides with anti-metastatic and anti-angiogenic activity due to its potent inhibition of heparanase and heparan sulfate-dependent angiogenic growth factors. It was recently in Phase III clinical trials for postresection hepatocellular carcinoma. The major oligosaccharide constituents of PI-88 were prepared for the first time by sulfonation of individually purified phosphorylated oligosaccharides isolated from the PI-88 precursor. PI-88 and its components were subjected to detailed 1D and 2D NMR spectroscopic analysis. The spectra of the individual components greatly assisted the assignment of minor resonances in the 1H NMR spectrum of PI-88. The data also showed that the majority of the oligosaccharides in PI-88 are fully sulfated and that undersulfated species present are largely due to anomeric desulfation. The solution conformation of the phosphomannopentaose sulfate (major component) of PI-88 was then determined by a combination of molecular dynamics simulations and NOE measurements which may provide insights into its binding interactions with target proteins.

Journal Title
Glycobiology
Conference Title
Book Title
Edition
Volume
Issue
Thesis Type
Degree Program
School
Publisher link
Patent number
Funder(s)
Grant identifier(s)
Rights Statement
Rights Statement
Item Access Status
Note
Access the data
Related item(s)
Subject
Biological sciences
Biomedical and clinical sciences
Persistent link to this record
Citation
Collections