TY - CHAP
T1 - Rational Design of Activity-Based Retaining β-Exoglucosidase Probes
AU - Li, Kah-Yee
AU - Kallemeijn, Wouter W.
AU - Jiang, Jianbing
AU - Walvoort, Marthe
AU - Willems, Lianne
AU - Beenakker, Thomas JM
AU - Van Den Elst, Hans
AU - Van Der Marel, Gijs
AU - Codée, Jeroen D C
AU - Aerts, Hans
AU - Florea, Bogdan I.
AU - Boot, Rolf G.
AU - Witte, Martin
AU - Overkleeft, Herman S.
PY - 2014/10/6
Y1 - 2014/10/6
N2 - Activity-based probes (ABPs) have been developed for numerous serine hydrolases, cysteine proteases, and threonine hydrolases, but less frequently for other enzyme families. This chapter details the successful development and application of a number of activity-based retaining β-exoglucosidase probes. It discusses how, by rational design, suitable ABPs for retaining β-exoglucosidases can be designed. Mutations in the gene encoding glucosidase, beta, acid (GBA) can lead to partial malfunctioning of the enzyme, leading to accumulation of its substrate, glucosylceramide. This is in a nutshell the basis of the lysosomal storage disorder, Gaucher disease. The aziridine-based scaffold holds more promise, and as one can learn from Cazypedia, there are numerous retaining exoglycosidases that follow the general Koshland mechanism and that are, in principle, amenable to ABPP activity-based protein profiling using cyclitol aziridines emulating in configuration and substitution pattern the corresponding substrate glycosides.
AB - Activity-based probes (ABPs) have been developed for numerous serine hydrolases, cysteine proteases, and threonine hydrolases, but less frequently for other enzyme families. This chapter details the successful development and application of a number of activity-based retaining β-exoglucosidase probes. It discusses how, by rational design, suitable ABPs for retaining β-exoglucosidases can be designed. Mutations in the gene encoding glucosidase, beta, acid (GBA) can lead to partial malfunctioning of the enzyme, leading to accumulation of its substrate, glucosylceramide. This is in a nutshell the basis of the lysosomal storage disorder, Gaucher disease. The aziridine-based scaffold holds more promise, and as one can learn from Cazypedia, there are numerous retaining exoglycosidases that follow the general Koshland mechanism and that are, in principle, amenable to ABPP activity-based protein profiling using cyclitol aziridines emulating in configuration and substitution pattern the corresponding substrate glycosides.
KW - Activity-based probes (ABPs)
KW - Activity-based retaining β-exoglucosidase probes
KW - Cyclophellitol aziridine
KW - GBA
UR - http://www.scopus.com/inward/record.url?scp=84926399717&partnerID=8YFLogxK
U2 - 10.1002/9783527687503.ch13
DO - 10.1002/9783527687503.ch13
M3 - Chapter
AN - SCOPUS:84926399717
SN - 9783527336111
SP - 191
EP - 206
BT - Concepts and Case Studies in Chemical Biology
PB - Wiley-Blackwell
ER -