Open AccessSimple Strategy for Taming Membrane-Disrupting Antibiotics
Author(s) -
Yuming Yu,
Mary J. Sabulski,
Wiley A. Schell,
Marcos M. Pires,
John R. Perfect,
Steven L. Regen
Publication year - 2016
Publication title -
bioconjugate chemistry
Language(s) - Uncategorized
Resource type - Journals
SCImago Journal Rank - 1.279
H-Index - 172
eISSN - 1520-4812
pISSN - 1043-1802
DOI - 10.1021/acs.bioconjchem.6b00629
Subject(s) - chemistry , cholic acid , antibiotics , membrane , amphiphile , covalent bond , boronic acid , sterol , selectivity , amphotericin b , combinatorial chemistry , antifungal , biochemistry , bile acid , organic chemistry , microbiology and biotechnology , cholesterol , catalysis , copolymer , biology , polymer
A strategy has been devised for increasing the cellular selectivity of membrane-disrupting antibiotics based on the attachment of a facially amphiphilic sterol. Using Amphotericin B (AmB) as a prototype, covalent attachment of cholic acid bound to a series of α,ω-diamines has led to a dramatic reduction in hemolytic activity, a significant reduction in toxicity toward HEK293T cells, and significant retention of antifungal activity.