Modified minimal-size fragments of heparan sulfate as inhibitors of endosulfatase-2 (Sulf-2).

Kennett A., Epple S., van der Valk G., Georgiou I., Gout E., Vivès RR., Russell AJ.

Sulf-2 has been identified as a putative target for anticancer therapies. Here we report the design and synthesis of sulfated disaccharide inhibitors based on IdoA(2S)-GlcNS(6S). Trisulfated disaccharide inhibitor IdoA(2S)-GlcNS(6Sulfamate) demonstrated potent Sulf-2 inhibition. The IC50 value was determined to be 39.8 μM ± 18.3, which is comparable to a tetrasaccharide inhibitor of HSulf-1 reported in the literature. We propose that the disaccharide IdoA(2S)-GlcNS(6S) is the shortest fragment size required for effective inhibition of the Sulfs.

DOI

10.1039/d3cc02565a

Type

Journal article

Publication Date

2024-01-04T00:00:00+00:00

Volume

60

Pages

436 - 439

Total pages

3

Keywords

Heparan Sulfate, Oligosaccharides, Disaccharides, Sulfotransferases

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