Brown James R D, Pintre Inmaculada C, Webb Simon J
Manchester Institute of Biotechnology (MIB) and School of Chemistry, University of Manchester, 131 Princess St., Manchester M1 7DN, UK.
Org Biomol Chem. 2014 Apr 28;12(16):2576-83. doi: 10.1039/c4ob00165f.
Wulff-type boronic acids have been shown to act as ionophores at pH 8.2 by transporting Na(+) through phospholipid bilayers. A cholate-boronic acid conjugate was synthesised and shown to be an ionophore, although the hydroxyl-lined face of the cholate moiety did not enhance ion transport. Mechanistic studies suggested a carrier mechanism for Na(+) transport. The addition of fructose (>5 mM) strongly inhibited ionophoric activity of the cholate-boronic acid conjugate, mirrored by a strong decrease in the ability of this compound to partition into an organic phase. Modelling of the partitioning and ion transport data, using a fructose/boronic acid binding constant measured at pH 8.2, showed a good correlation with the extent of fructose/boronic acid complexation and suggested high polarity fructose/boronic acid complexes are poor ionophores. The sensitivity of ion transport to fructose implies that boronic acid-based antibiotic ionophores with activity modulated by polysaccharides in the surrounding environment may be accessible.
伍尔夫型硼酸已被证明在pH 8.2时通过磷脂双层转运Na⁺而充当离子载体。合成了一种胆酸盐 - 硼酸共轭物，它被证明是一种离子载体，尽管胆酸盐部分的羟基内衬面并未增强离子转运。机理研究表明Na⁺转运存在载体机制。加入果糖（>5 mM）强烈抑制胆酸盐 - 硼酸共轭物的离子载体活性，同时该化合物分配到有机相的能力也大幅下降。利用在pH 8.2时测得的果糖/硼酸结合常数对分配和离子转运数据进行建模，结果表明果糖/硼酸络合程度与之具有良好的相关性，并表明高极性的果糖/硼酸络合物是较差的离子载体。离子转运对果糖的敏感性表明基于硼酸的抗生素离子载体可能可以实现，其活性可由周围环境中的多糖调节。
