title: Fructose controlled ionophoric activity of a cholate-boronic acid.
abstract: 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.
authors.affiliation: Manchester Institute of Biotechnology (MIB) and School of Chemistry, University of Manchester, 131 Princess St., Manchester M1 7DN, UK. S.Webb@manchester.ac.uk.
authors.forename: James R D
authors.initials: JR
authors.lastname: Brown
authors.forename: Inmaculada C
authors.initials: IC
authors.lastname: Pintre
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Webb
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry*; D001897:Boronic Acids / Q000737:chemistry*; D020355:Cholates / Q000737:chemistry*; D005632:Fructose / Q000737:chemistry*; D007476:Ionophores / Q000737:chemistry*; D015394:Molecular Structure; D011134:Polysaccharides / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; D001897:Boronic Acids; D020355:Cholates; D007476:Ionophores; D011134:Polysaccharides; D005632:Fructose