Exploiting sp2 -Hybridisation in the Development of Potent 1,5-α-l-Arabinanase Inhibitors

Travis Coyle; Aleksandra W Debowski; Annabelle Varrot; Keith A Stubbs

doi:10.1002/cbic.201700073

Exploiting sp² -Hybridisation in the Development of Potent 1,5-α-l-Arabinanase Inhibitors

Chembiochem. 2017 Jun 1;18(11):974-978. doi: 10.1002/cbic.201700073. Epub 2017 Apr 20.

Authors

Travis Coyle^{1

2}, Aleksandra W Debowski^{1

3}, Annabelle Varrot⁴, Keith A Stubbs¹

Affiliations

¹ School of Molecular Sciences, University of Western Australia, 35 Stirling Highway, Crawley, WA, 6009, Australia.
² Present address: School of Chemistry, University College Dublin, Stillorgan Road, Belfield, Dublin, 4, Ireland.
³ School of Biomedical Sciences, University of Western Australia, 35 Stirling Highway, Crawley, WA, 6009, Australia.
⁴ CERMAV, Université Grenoble Alpes, CNRS, 38000, Grenoble, France.

PMID: 28266777
DOI: 10.1002/cbic.201700073

Abstract

The synthesis of potent inhibitors of GH93 arabinanases as well as a synthesis of a chromogenic substrate to measure GH93 arabinanase activity are described. An insight into the reasons behind the potency of the inhibitors was gained through X-ray crystallographic analysis of the arabinanase Arb93A from Fusarium graminearum. These compounds lay a foundation for future inhibitor development as well as for the use of the chromogenic substrate in biochemical studies of GH93 arabinanases.

Keywords: arabinanases; carbamate; chromogenic substrate; enzyme inhibitors; hydroximolactone.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Chromogenic Compounds / chemical synthesis
Crystallography, X-Ray
Enzyme Inhibitors / chemical synthesis
Fusarium / chemistry*
Glycoside Hydrolases / antagonists & inhibitors*
Models, Molecular
Structure-Activity Relationship

Substances

Chromogenic Compounds
Enzyme Inhibitors
Glycoside Hydrolases
alpha-N-arabinofuranosidase