6‐Amino‐6‐deoxy‐5,6‐di‐N‐(N′‐octyliminomethylidene)nojirimycin: Synthesis,Biological Evaluation,and Crystal Structure in Complex with Acid β‐Glucosidase
1. Department of Structural Biology, Weizmann Institute of Science, Rehovot 76100 (Israel);2. Departamento de Química Orgánica, Facultad de Química, Universidad de Sevilla, Profesor García González 1, 41012 Seville (Spain), Fax: (+34)?954624960;3. Instituto de Investigaciones Químicas, CSIC–Universidad de Sevilla, Américo Vespucio 49, Isla de la Cartuja, 41092 Seville (Spain);4. Department of Neurobiology, Weizmann Institute of Science, Rehovot 76100 (Israel);5. Protalix Biotherapeutics, 2 Snunit Street, Science Park, Carmiel 20100 (Israel);6. Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100 (Israel), Fax: (+972)?8‐9344112
Abstract:
6‐Amino‐6‐deoxy‐5,6‐di‐ N ‐( N ′‐octyliminomethylidene)nojirimycin , a reducing analogue of N‐nonyl‐1‐deoxynojirimycin, proved to be a potent and very selective inhibitor of β‐glucosidases, including human acid β‐glucosidase. Structural studies of the enzyme–inhibitor complex showed a binding mode in which the anomeric hydroxy group is accommodated in the “wrong” α configuration.
