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dc.contributor.authorFuente, Alex de laes_ES
dc.contributor.authorRísquez-Cuadro, Rocioes_ES
dc.contributor.authorVerdaguer, Xavieres_ES
dc.contributor.authorGarcía-Fernández, José Manueles_ES
dc.contributor.authorNanba, Ejies_ES
dc.contributor.authorHigaki, Katsumies_ES
dc.contributor.authorOrtiz-Mellet, Carmenes_ES
dc.contributor.authorRiera, Antonies_ES
dc.identifier.citationEuropean Journal of Medicinal Chemistry, 121: 926-938 (2016)es_ES
dc.description.abstractDue to their capacity to inhibit hexosaminidases, 2-acetamido-1,2-dideoxy-iminosugars have been widely studied as potential therapeutic agents for various diseases. An efficient stereoselective synthesis of 2-acetamido-1,2-dideoxyallonojirimycin (DAJNAc), the most potent inhibitor of human placenta b-Nacetylglucosaminidase (b-hexosaminidase) among the epimeric series, is here described. This novel procedure can be easily scaled up, providing enough material for structural modifications and further biological tests. Thus, two series of sp2-iminosugar conjugates derived from DAJNAc have been prepared, namely monocyclic DAJNAc-thioureas and bicyclic 2-iminothiazolidines, and their glycosidase inhibitory activity evaluated. The data evidence the utmost importance of developing diversity-oriented synthetic strategies allowing optimization of electrostatic and hydrophobic interactions to achieve high inhibitory potencies and selectivities among isoenzymes. Notably, strong differences in the inhibition potency of the compounds towards b-hexosaminidase from human placenta (mature) or cultured fibroblasts (precursor form) were encountered. The ensemble of data suggests that the ratio between them, and not the inhibition potency towards the placenta enzyme, is a good indication of the chaperoning potential of TaySachs disease-associated mutant hexosaminidasees_ES
dc.relation.isversionofPublisher's versiones_ES
dc.subjectHexosaminidase inhibitorses_ES
dc.subjectStereoselective synthesises_ES
dc.subjectPharmacological chaperoneses_ES
dc.subjectTay-Sachs diseasees_ES
dc.titleEfficient stereoselective synthesis of 2-acetamido-1,2- dideoxyallonojirimycin (DAJNAc) and sp2-iminosugar conjugates: Novel hexosaminidase inhibitors with discrimination capabilities between the mature and precursor forms of the enzymees_ES
dc.description.peerreviewedPeer reviewedes_ES
oprm.item.hasRevisionno ko 0 false*
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