6-Amino-6-deoxy-5,6-di-N-(N′-octyliminomethylidene)nojirimycin: Synthesis, Biological Evaluation, and Crystal Structure in Complex with Acid β-Glucosidase

6 páginas, 4 figuras, 2 tablas, 1 esquema6-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.We thank the Spanish Ministerio de Educación y Ciencia (contract numbers CTQ2006-15515-C02-01/BQU and CTQ2007-61180/PPQ), the Junta de Andalucía, the EC VIth Framework Programme ('SPINE2-COMPLEXES' Project, Contract 03 122, and “Teach-SG” Project, Contract ISSG-CT-2007–037 198), and the Bruce Rosen, William Singer, Divadol, and Neuman Foundations for financial support.Peer reviewe

6-Amino-6-deoxy-5,6-di- N

6 páginas, 4 figuras, 2 tablas, 1 esquema6-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.We thank the Spanish Ministerio de Educación y Ciencia (contract numbers CTQ2006-15515-C02-01/BQU and CTQ2007-61180/PPQ), the Junta de Andalucía, the EC VIth Framework Programme ('SPINE2-COMPLEXES' Project, Contract 03 122, and “Teach-SG” Project, Contract ISSG-CT-2007–037 198), and the Bruce Rosen, William Singer, Divadol, and Neuman Foundations for financial support.Peer reviewe