| DOI | Trouver le DOI : https://doi.org/10.1002/cbic.200800550 |
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| Auteur | Rechercher : Sisu, Cristina; Rechercher : Baron, Andrew J.; Rechercher : Branderhorst, Hilbert M.; Rechercher : Connell, Simon D.; Rechercher : Weijers, Carel A. G. M.; Rechercher : de Vries, Renko; Rechercher : Hayes, Edward D.; Rechercher : Pukin, Aliaksei V.; Rechercher : Gilbert, Michel1; Rechercher : Pieters, Roland J.; Rechercher : Zuilhof, Han; Rechercher : Visser, Gerben M.; Rechercher : Turnbull, W. Bruce |
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| Affiliation | - Conseil national de recherches du Canada. Institut des sciences biologiques du CNRC
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| Format | Texte, Article |
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| Sujet | aggregation; carbohydrates; cholera; dendrimers; multivalency |
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| Résumé | Divalent and tetravalent analogues of ganglioside GM1 are potent inhibitors of cholera toxin and Escherichia coli heat-labile toxin. However, they show little increase in inherent affinity when compared to the corresponding monovalent carbohydrate ligand. Analytical ultracentrifugation and dynamic light scattering have been used to demonstrate that the multivalent inhibitors induce protein aggregation and the formation of space-filling networks. This aggregation process appears to arise when using ligands that do not match the valency of the protein receptor. While it is generally accepted that multivalency is an effective strategy for increasing the activity of inhibitors, here we show that the valency of the inhibitor also has a dramatic effect on the kinetics of aggregation and the stability of intermediate protein complexes. Structural studies employing atomic force microscopy have revealed that a divalent inhibitor induces head-to-head dimerization of the protein toxin en route to higher aggregates. |
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| Date de publication | 2009-01-26 |
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| Dans | |
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| Langue | anglais |
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| Publications évaluées par des pairs | Oui |
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| Numéro NPARC | 19068094 |
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| Exporter la notice | Exporter en format RIS |
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| Signaler une correction | Signaler une correction (s'ouvre dans un nouvel onglet) |
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| Identificateur de l’enregistrement | f61f2dc7-16e6-45d7-86c3-74b2e2f4e009 |
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| Enregistrement créé | 2011-12-14 |
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| Enregistrement modifié | 2020-04-16 |
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