Micelle/monomer control over the membrane-disrupting properties of an amphiphilic antibiotic

Article abstract of DOI:10.1021/ja00128a011

A homologous series of amphotericin B-oligo(ethylene glycol) conjugates has been synthesized, via condensation of the carboxylic acid group of amphotericin B with oligo(ethylene glycol)-substituted amines [NH₂(CH₂-CH₂O)(n)CH₃, where n = 1, 6, 15], and examined with respect to their aggregation properties and their ability to disrupt the membrane integrity of Candida albicans and human red blood cells. Incremental increase in the size of the oligo(ethylene glycol) moiety leads to a significant increase in the critical micelle concentration of the macrolide and to a corresponding increase in the concentration that is required for hemolysis. In sharp contrast, the same increase in oligo(ethylene glycol) size affords only a modest reduction in antifungal activity; the net result is a separation of antifungal and hemolytic activity. These results clearly highlight the need for taking into account the aggregation properties of membrane-disrupting antibiotics with respect to target recognition and specificity and also with regard to rational molecular design.