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

TY - JOUR

T1 - Glycosylated cyclophellitol-derived activity-based probes and inhibitors for cellulases

AU - De Boer, Casper

AU - McGregor, Nicholas George Sarre

AU - Peterse, Evert

AU - Schröder, Sybrin P

AU - Florea, Bogdan I.

AU - Jiang, Jianbing

AU - Reijngoud, Jos

AU - Ram, Arthur F.J.

AU - Van Der Marel, Gijsbert A.

AU - Van Wezel, Gilles P.

AU - Codee, Jeroen D. C.

AU - Overkleeft, Herman S.

AU - Davies, Gideon John

N1 - © The Royal Society of Chemistry 2020

PY - 2020/7/28

Y1 - 2020/7/28

N2 - 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.

AB - 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.

U2 - 10.1039/D0CB00045K

DO - 10.1039/D0CB00045K

M3 - Article

SN - 2633-0679

VL - 1

SP - 148

EP - 155

JO - RSC Chemical Biology

JF - RSC Chemical Biology

IS - 3

ER -