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Glycosylated cyclophellitol-derived activity-based probes and inhibitors for cellulases

DOI: 10.1039/D0CB00045K DOI Help

Authors: Casper De Boer (Leiden University) , Nicholas G. S. Mcgregor (The University of York) , Evert Peterse (Leiden University) , Sybrin P. Schröder (Leiden University) , Bogdan I. Florea (Leiden University) , Jianbing Jiang (Leiden University) , Jos Reijngoud (Leiden University) , Arthur F. J. Ram (Leiden University) , Gilles P. Van Wezel (Leiden University) , Gijsbert A. Van Der Marel (Leiden University) , Jeroen D. C. Codée (Leiden University) , Herman S. Overkleeft (Leiden University) , Gideon Davies (The University of York)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Rsc Chemical Biology , VOL 25

State: Published (Approved)
Published: July 2020
Diamond Proposal Number(s): 18598

Open Access Open Access

Abstract: Cellulases and related β-1,4-glucanases are essential components of lignocellulose-degrading enzyme mixtures. The detection of β-1,4-glucanase activity typically relies on monitoring the breakdown of purified lignocellulose-derived substrates or synthetic chromogenic substrates, limiting the activities which can be detected and complicating the tracing of activity back to specific components within complex enzyme mixtures. As a tool for the rapid detection and identification of β-1,4-glucanases, a series of glycosylated cyclophellitol inhibitors mimicking β-1,4-glucan oligosaccharides have been synthesised. These compounds are highly efficient inhibitors of HiCel7B, a well-known GH7 endo-β-1,4-glucanase. An elaborated activity-based probe facilitated the direct detection and identification of β-1,4-glucanases within a complex fungal secretome without any detectable cross-reactivity with β-D-glucosidases. These probes and inhibitors add valuable new capacity to the growing toolbox of cyclophellitol-derived probes for the activity-based profiling of biomass-degrading enzymes.

Subject Areas: Chemistry, Biology and Bio-materials

Instruments: I03-Macromolecular Crystallography