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Synthesis and evaluation of 2-deoxy-2-amino-β-cellobiosides as cellulase inhibitors

Tom Desmet (UGent) , Marc Claeyssens (UGent) , Kathleen Piens (UGent) and Wim Nerinckx (UGent)
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Abstract
The cellulase mixture of Hypocrea jecorina (formerly Trichoderma reesei) contains a variety of exo- and endoglucanases that belong to different structural families. As such, these enzymes form an interesting model system to study the enzyme-ligand interactions in glycoside hydrolases. The nucleophilic carboxylate of retaining -glycosidases is believed to form a hydrogen bond with the 2-hydroxyl group of their substrate. Consequently, replacing this hydroxyl group with an amino group should result in a stronger electrostatic interaction and thus an increased affinity for the ligand. In this study, several modified cellobiosides were synthesized and evaluated as cellulase inhibitors. The introduction of an amino group was found to have an unpredictable effect on the inhibitory power of the ligands. However, the enzymes display a very high affinity for the corresponding 2-azido compounds, precursors in the synthetic route. The new ligand m-iodobenzyl 2-deoxy-2-azido--cellobioside even is the strongest inhibitor of cellobiohydrolase I known to date (KI= 1 M).
Keywords
2-Amino-2-deoxy-cellobioside, TRICHODERMA-REESEI, Inhibition, Cellulase, Glycosidase, AZIDONITRATION, ENDOGLUCANASE, HYDROLYSIS, MECHANISMS, GLYCOSIDES, CLEAVAGE, GLUCOSE, ENZYMES

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Chicago
Desmet, Tom, Marc Claeyssens, Kathleen Piens, and Wim Nerinckx. 2010. “Synthesis and Evaluation of 2-deoxy-2-amino-β-cellobiosides as Cellulase Inhibitors.” Journal of Carbohydrate Chemistry 29 (4): 164–180.
APA
Desmet, Tom, Claeyssens, M., Piens, K., & Nerinckx, W. (2010). Synthesis and evaluation of 2-deoxy-2-amino-β-cellobiosides as cellulase inhibitors. JOURNAL OF CARBOHYDRATE CHEMISTRY, 29(4), 164–180.
Vancouver
1.
Desmet T, Claeyssens M, Piens K, Nerinckx W. Synthesis and evaluation of 2-deoxy-2-amino-β-cellobiosides as cellulase inhibitors. JOURNAL OF CARBOHYDRATE CHEMISTRY. 2010;29(4):164–80.
MLA
Desmet, Tom, Marc Claeyssens, Kathleen Piens, et al. “Synthesis and Evaluation of 2-deoxy-2-amino-β-cellobiosides as Cellulase Inhibitors.” JOURNAL OF CARBOHYDRATE CHEMISTRY 29.4 (2010): 164–180. Print.
@article{1089300,
  abstract     = {The cellulase mixture of Hypocrea jecorina (formerly Trichoderma reesei) contains a variety of exo- and endoglucanases that belong to different structural families. As such, these enzymes form an interesting model system to study the enzyme-ligand interactions in glycoside hydrolases. The nucleophilic carboxylate of retaining -glycosidases is believed to form a hydrogen bond with the 2-hydroxyl group of their substrate. Consequently, replacing this hydroxyl group with an amino group should result in a stronger electrostatic interaction and thus an increased affinity for the ligand. In this study, several modified cellobiosides were synthesized and evaluated as cellulase inhibitors. The introduction of an amino group was found to have an unpredictable effect on the inhibitory power of the ligands. However, the enzymes display a very high affinity for the corresponding 2-azido compounds, precursors in the synthetic route. The new ligand m-iodobenzyl 2-deoxy-2-azido--cellobioside even is the strongest inhibitor of cellobiohydrolase I known to date (KI= 1 M).},
  author       = {Desmet, Tom and Claeyssens, Marc and Piens, Kathleen and Nerinckx, Wim},
  issn         = {0732-8303},
  journal      = {JOURNAL OF CARBOHYDRATE CHEMISTRY},
  keyword      = {2-Amino-2-deoxy-cellobioside,TRICHODERMA-REESEI,Inhibition,Cellulase,Glycosidase,AZIDONITRATION,ENDOGLUCANASE,HYDROLYSIS,MECHANISMS,GLYCOSIDES,CLEAVAGE,GLUCOSE,ENZYMES},
  language     = {eng},
  number       = {4},
  pages        = {164--180},
  title        = {Synthesis and evaluation of 2-deoxy-2-amino-\ensuremath{\beta}-cellobiosides as cellulase inhibitors},
  url          = {http://dx.doi.org/10.1080/07328303.2010.508142},
  volume       = {29},
  year         = {2010},
}

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