Biofunctionalized surfactant mesophases as polyvalent inhibitors of cholera toxin

Bioconjug Chem. 2007 Sep-Oct;18(5):1442-9. doi: 10.1021/bc0700640. Epub 2007 Aug 24.

Abstract

The cubic lyotropic mesophase composed of the ganglioside G(M1) and the synthetic surfactant phytantriol has been employed as a scaffold to prepare a polyvalent inhibitor of cholera toxin (CT). Surfactant mixtures containing up to 20% (w/w) G(M1)/phytantriol afforded a hydrated insoluble gel-like material, which retained an inverse cubic phase (Q) structure in excess water and at 22 degrees C, as confirmed using small-angle X-ray scattering. The G(M1)-functionalized mesophases bind up to 98.8% of CT from solution containing 100 ng/mL of CT with a dissociation constant (K(d)) of 67-73 nM. The estimated IC50 values for the mesophase systems were 0.1-0.27 microM. The inhibitory effect of the mesophases may be enhanced through the high internal surface area of the inverse cubic phase in addition to the optimal self-orientation of G(M1) ligand to match the distribution of binding sites on the toxin surface. As a result, polyvalent inhibitor materials manufactured using these mesophase structures do not require precise control of ligand distribution, which offers advantages with respect to complexity of synthesis and formulation when compared to more rigid and conformationally restricted materials. This approach provides a route to a unique class of polyvalent inhibitors, which should be broadly applicable to a range of bacterial and plant toxins.

MeSH terms

  • Antitoxins / chemistry*
  • Cholera Toxin / antagonists & inhibitors*
  • Fatty Alcohols / chemistry*
  • G(M1) Ganglioside / chemistry*
  • Scattering, Small Angle
  • Surface-Active Agents / chemistry*
  • Temperature
  • Toxins, Biological / antagonists & inhibitors*
  • Water / chemistry
  • X-Ray Diffraction

Substances

  • Antitoxins
  • Fatty Alcohols
  • Surface-Active Agents
  • Toxins, Biological
  • Water
  • G(M1) Ganglioside
  • 3,7,11,15-tetramethyl-1,2,3-hexadecanetriol
  • Cholera Toxin