Biofunctionalized Surfactant Mesophases as Polyvalent Inhibitors of Cholera Toxin

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• 作者：Anastasios Polyzos ; Malcolm R. Alderton ; Raymond M. Dawson ; Patrick G. Hartley
• 刊名：Bioconjugate Chemistry
• 出版年：2007
• 出版时间：September 2007
• 年：2007
• 卷：18
• 期：5
• 页码：1442 - 1449
• 全文大小：318K
• 年卷期：v.18,no.5(September 2007)
• ISSN：1520-4812

文摘

The cubic lyotropic mesophase composed of the ganglioside G_M1 and the synthetic surfactant phytantriol hasbeen employed as a scaffold to prepare a polyvalent inhibitor of cholera toxin (CT). Surfactant mixtures containingup to 20% (w/w) G_M1/phytantriol afforded a hydrated insoluble gel-like material, which retained an inverse cubicphase (Q) structure in excess water and at 22 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 dissociationconstant (K_d) of 67-73 nM. The estimated IC₅₀ values for the mesophase systems were 0.1-0.27 M. The inhibitoryeffect of the mesophases may be enhanced through the high internal surface area of the inverse cubic phase inaddition to the optimal self-orientation of G_M1 ligand to match the distribution of binding sites on the toxinsurface. As a result, polyvalent inhibitor materials manufactured using these mesophase structures do not requireprecise control of ligand distribution, which offers advantages with respect to complexity of synthesis andformulation when compared to more rigid and conformationally restricted materials. This approach provides aroute to a unique class of polyvalent inhibitors, which should be broadly applicable to a range of bacterial andplant toxins.