Artículo
Understanding multivalent effects in glycosidase inhibition using C-glycoside click clusters as molecular probes
Autor/es | Stauffert, Fabien
Bodlenner, Anne Nguyet Trinh, Thi Minh García Moreno, M. Isabel Ortiz Mellet, Carmen Nierengarten, Jean François Compain, Philippe |
Departamento | Universidad de Sevilla. Departamento de Química orgánica |
Fecha de publicación | 2016 |
Fecha de depósito | 2022-05-31 |
Publicado en |
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Resumen | The synthesis of the first examples of multivalent C-glycosides based on C60-fullerene or β-cyclodextrin cores by way of Cu(I)-catalyzed azide–alkyne cycloadditions is reported. These compounds were designed as molecular ... The synthesis of the first examples of multivalent C-glycosides based on C60-fullerene or β-cyclodextrin cores by way of Cu(I)-catalyzed azide–alkyne cycloadditions is reported. These compounds were designed as molecular probes to understand the mechanisms underlying the outstanding multivalent effects observed in glycosidase inhibition. The inhibition results obtained support a multivalent-binding model based on two scenarios both involving nonspecific interactions and varying by the presence or the absence of active site specific interactions. The magnitude of the multivalent effect obtained depends on the identity of the glycosidase involved and more specifically on the accessibility of its catalytic active site. Large inhibitory multivalent effects can be obtained when both glycosidase active sites and non-catalytic sites at the protein surface are involved in binding events. On the other hand, nonspecific interactions alone are not sufficient to achieve relative affinity enhancements exceeding a simple statistical effect (i.e., a relative inhibition potency not better than one on a valence-corrected basis). |
Agencias financiadoras | Ministerio de Economía y Competitividad (MINECO). España European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER) European Commission. Fondo Social Europeo (FSO) |
Identificador del proyecto | SAF2013-44021-R |
Cita | Stauffert, F., Bodlenner, A., Nguyet Trinh, T.M., García Moreno, M.I., Ortiz Mellet, C., Nierengarten, J.F. y Compain, P. (2016). Understanding multivalent effects in glycosidase inhibition using C-glycoside click clusters as molecular probes. New Journal of Chemistry, 40 (9), 7421-7430. |
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