| Literature DB >> 15157878 |
Nobuaki Matsumori1, Noritsugu Eiraku, Shigeru Matsuoka, Tohru Oishi, Michio Murata, Takaaki Aoki, Toru Ide.
Abstract
Amphotericin B-sterol conjugates were synthesized and examined for their membrane permeabilizing activity. Ergosterol and cholesterol, each connected with amphotericin B via an ethylenecarbamate or hexamethylenecarbamate linker, were examined by K(+) flux assays using liposomes and by single-channel recording across phospholipid membrane. Among four conjugates tested, AmB-ergosterol bearing an ethylenecarbamate linker exhibited the most powerful activity, which substantially exceeded that of the cholesterol homolog. Single-channel recording clearly exhibited that the ergosterol conjugate elicited channel current with the conductance of 28 pS, which was comparable with those by AmB, and revealed a higher channel open probability than the cholesterol conjugate. These results imply that direct interaction between amphotericin B and ergosterol is reproduced by their conjugate, which may serve as a model compound for understanding the drug's selective toxicity.Entities:
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Year: 2004 PMID： 15157878 DOI： 10.1016/j.chembiol.2004.02.027
Source DB: PubMed Journal: Chem Biol ISSN： 1074-5521