An amphotericin B-ergosterol covalent conjugate with powerful membrane permeabilizing activity.
An amphotericin B-ergosterol covalent conjugate with powerful membrane permeabilizing activity.
复制标题
DOI：
10.1016/j.chembiol.2004.02.027
复制
发表时间：
2004-05
影响因子：
--
通讯作者：
N. Matsumori;N. Eiraku;S. Matsuoka;T. Oishi;M. Murata;T. Aoki;T. Ide
中科院分区：
文献类型：
--
作者：
N. Matsumori;N. Eiraku;S. Matsuoka;T. Oishi;M. Murata;T. Aoki;T. Ide
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.
