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A reverse-phase HPLC assay for measuring the interaction of polyene macrolide antifungal agents with sterols

✍ Scribed by Bradley J. Backes; Scott D. Rychnovsky


Book ID
102630889
Publisher
Elsevier Science
Year
1992
Tongue
English
Weight
449 KB
Volume
205
Category
Article
ISSN
0003-2697

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✦ Synopsis


A quick and simple affinity chromatography method for gauging the interaction of polyene antifungal agents with sterols has been developed. The required affinity columns are prepared from a standard C-18 reverse-phase HPLC column by injecting a measured quantity of sterol under conditions where it is completely retained. After the assay, the sterol is eluted with a less polar solvent and the column reused. By comparing the elution volume of a polyene injected onto the sterol-free column (Ve) with that of the polyene injected onto the sterol-doped column (V), an association constant (Ka) for the polyene-sterol complex was determined. Association constants of different amphotericin B-sterol and pimaricin-sterol complexes were determined and correlated with the polyene's ability to induce membrane permeability and its antifungal properties. This procedure provides a new tool for screening polyene macrolides for antifungal therapy.