» Articles » PMID: 17967543

Synthesis and Heparanase Inhibitory Activity of Sulfated Mannooligosaccharides Related to the Antiangiogenic Agent PI-88

Overview
Journal Bioorg Med Chem
Specialties Biochemistry
Chemistry
Date 2007 Oct 31
PMID 17967543
Citations 14
Authors
Affiliations
Soon will be listed here.
Abstract

A stepwise synthetic route to the mannooligosaccharides from the neutral fraction of Pichia holstii phosphomannan hydrolysate, including a tetrasaccharylamine component, was developed using only two or three readily available d-mannose building blocks. These compounds were sulfonated to give the corresponding sulfated oligosaccharides which are closely related to the constituents of the anticancer agent PI-88. The synthetic approach is well suited to the preparation of analogues as demonstrated by the synthesis of a series of (1-->3)-linked mannooligosaccharides. The inhibitory activity of the sulfated oligosaccharides against heparanase was determined using a Microcon ultrafiltration assay. The tetra- and pentasaccharides were potent competitive inhibitors of heparanase (K(i)=200-280nM) whilst the shorter di- and trisaccharides were partial competitive inhibitors and did not completely inhibit the enzyme even at very high concentrations.

Citing Articles

Structural Insights into Pixatimod (PG545) Inhibition of Heparanase, a Key Enzyme in Cancer and Viral Infections.

Chhabra M, Wilson J, Wu L, Davies G, Gandhi N, Ferro V Chemistry. 2022; 28(11):e202104222.

PMID: 34981584 PMC: 9303737. DOI: 10.1002/chem.202104222.


From Cancer to COVID-19: A Perspective on Targeting Heparan Sulfate-Protein Interactions.

Chhabra M, Doherty G, See N, Gandhi N, Ferro V Chem Rec. 2021; 21(11):3087-3101.

PMID: 34145723 PMC: 8441866. DOI: 10.1002/tcr.202100125.


A Concise Synthesis of a BODIPY-Labeled Tetrasaccharide Related to the Antitumor PI-88.

Ventura J, Uriel C, Gomez A, Avellanal-Zaballa E, Banuelos J, Garcia-Moreno I Molecules. 2021; 26(10).

PMID: 34068920 PMC: 8156587. DOI: 10.3390/molecules26102909.


Targeting Heparanase in Cancer: Inhibition by Synthetic, Chemically Modified, and Natural Compounds.

Mohan C, Hari S, Preetham H, Rangappa S, Barash U, Ilan N iScience. 2019; 15:360-390.

PMID: 31103854 PMC: 6548846. DOI: 10.1016/j.isci.2019.04.034.


The Development of Assays for Heparanase Enzymatic Activity: Towards a Gold Standard.

Chhabra M, Ferro V Molecules. 2018; 23(11).

PMID: 30441818 PMC: 6278452. DOI: 10.3390/molecules23112971.