Journal article
Dissection of Conformationally Restricted Inhibitors Binding to a β-Glucosidase
Glycosidase inhibition, important in the quest for highly potent and specific drugs, can be achieved by mimicking the oxocarbenium ion-like transition-state species that form during the catalytic mechanism. Castanospermine and calystegine B2 are potent inhibitors that are conformationally restricted by the inclusion of ethylene linkers.
Their binding to a β-glucosidase from Thermotoga maritima has been studied by structural, kinetic and thermodynamic methods. Although both compounds inhibit with a similar potency, castanospermine derives the majority of its energetic contribution from enthalpy whereas calystegine B2 binding is more entropically driven.
Language: | English |
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Publisher: | WILEY‐VCH Verlag |
Year: | 2006 |
Pages: | 738-742 |
ISSN: | 14397633 and 14394227 |
Types: | Journal article |
DOI: | 10.1002/cbic.200600005 |
ORCIDs: | Madsen, Robert |
Binding Sites Carbohydrate Conformation Crystallography, X-Ray Enzyme Inhibitors Hydrogen-Ion Concentration Kinetics Models, Molecular Molecular Conformation Protein Binding Protein Structure, Tertiary Structure-Activity Relationship beta-Glucosidase calystegine castanospermine glucosidase inhibitors transition state