Cristina Sisu

Publications (4)15.78 Total impact

• Article: The influence of ligand valency on aggregation mechanisms for inhibiting bacterial toxins.

  Cristina Sisu, Andrew J Baron, Hilbert M Branderhorst, Simon D Connell, Carel A G M Weijers, Renko de Vries, Edward D Hayes, Aliaksei V Pukin, Michel Gilbert, Roland J Pieters, Han Zuilhof, Gerben M Visser, W Bruce Turnbull
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  ABSTRACT: 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.
  ChemBioChem 12/2008; 10(2):329-37. · 3.94 Impact Factor
• Article: The Influence of Ligand Valency on Aggregation Mechanisms for Inhibiting Bacterial Toxins

  Cristina Sisu, Andrew J. Baron, Hilbert M. Branderhorst Dr, Simon D. Connell Dr, Carel A. G. M. Weijers Dr, Renko de Vries Dr, Edward D. Hayes, Aliaksei V. Pukin, Michel Gilbert Dr, Roland J. Pieters Dr, Han Zuilhof Prof. Dr, Gerben M. Visser Dr, W. Bruce Turnbull Dr
  ChemBioChem 11/2008; 10(2):329 - 337. · 3.94 Impact Factor
• Source

  Available from: uu.nl

  Article: Strong inhibition of cholera toxin by multivalent GM1 derivatives.

  Aliaksei V Pukin, Hilbert M Branderhorst, Cristina Sisu, Carel A G M Weijers, Michel Gilbert, Rob M J Liskamp, Gerben M Visser, Han Zuilhof, Roland J Pieters
  ChemBioChem 10/2007; 8(13):1500-3. · 3.94 Impact Factor
• Article: Strong Inhibition of Cholera Toxin by Multivalent GM1 Derivatives

  Aliaksei V. Pukin, Hilbert M. Branderhorst, Cristina Sisu, Carel A. G. M. Weijers Dr, Michel Gilbert Dr, Rob M. J. Liskamp Prof. Dr, Gerben M. Visser Dr, Han Zuilhof Prof. Dr, Roland J. Pieters Dr
  ChemBioChem 07/2007; 8(13):1500 - 1503. · 3.94 Impact Factor