Szponarski W, Wietzerbin J, Borowski E, Gary-Bobo C M
Département de Biologie, CEN Saclay, Gif-sur-Yvette.
Biochim Biophys Acta. 1988 Feb 8;938(1):97-106. doi: 10.1016/0005-2736(88)90126-5.
Four 14C-labelled amphotericin B (Am B) derivatives with different net electric charges were examined: zwitterionic N-fructosyl Am B, positively charged N-fructosyl Am B methyl ester, negatively charged N-acetyl Am B and neutral N-acetyl Am B methyl ester. The binding of these four derivatives to human red cells and their octanol-water partition coefficients were measured. Simple partitioning between red cells and buffer was found for the four compounds, regardless of concentration, within a range of 10(-8) and 10(-4) M. This indicates the absence of cooperativity and saturability of binding at least in this concentration range. The constant partition coefficients were found to be three to five times higher for the two methyl ester derivatives than for the two non-esterified compounds. All partition coefficients were proportional to those found for the octanol-water system. Efficiency in inducing K+ leak from red cells was measured during the binding experiments. Despite the higher partition coefficients of the two methyl ester derivatives, they were found to have much lower ionophoric efficiency than the two non-esterified compounds. These results are discussed in terms of the mechanism of permeability pathway formation by polyene antibiotics.
研究了四种带有不同净电荷的14C标记两性霉素B（Am B）衍生物：两性离子型N-果糖基两性霉素B、带正电荷的N-果糖基两性霉素B甲酯、带负电荷的N-乙酰基两性霉素B和中性的N-乙酰基两性霉素B甲酯。测定了这四种衍生物与人红细胞的结合情况及其正辛醇-水分配系数。在10(-8)至10(-4) M范围内，无论浓度如何，这四种化合物在红细胞和缓冲液之间均呈现简单的分配情况。这表明至少在该浓度范围内不存在结合的协同性和饱和性。发现两种甲酯衍生物的恒定分配系数比两种未酯化化合物高3至5倍。所有分配系数均与正辛醇-水体系中的分配系数成比例。在结合实验过程中测定了诱导红细胞钾离子泄漏的效率。尽管两种甲酯衍生物的分配系数较高，但发现它们的离子载体效率比两种未酯化化合物低得多。根据多烯抗生素形成通透性途径的机制对这些结果进行了讨论。
