Improving the membrane permeability of sialic acid derivatives.
The potential of boronic acids to improve the bioavailability of carbohydrate derived drugs was investigated through the study of the transport of four sialic acid derivatives through a lipophilic supported liquid membrane at departure phase pH's of 7.4, 8.5 and 10.0. It was found that facilitated transport did occur in most cases, but interestingly, and in contrast to that observed with monosaccharides such as d-fructose, the lipophilic ammonium salt, Aliquat 336, promoted fluxes than those of the boronic acid. The triol side chain of the sialic acid derivatives, combined with the amide at C5, appears to represent a previously unrecognised chloride binding domain which promotes extraction of these compounds into membranes containing Aliquat 336, leading to fluxes greater than those produced by boronic acids.
Altamore
Timothy M
TM
School of Chemistry, Monash University, Clayton, Melbourne, Victoria, Australia.
Duggan
Peter J
PJ
Krippner
Guy Y
GY
D001897:Boronic Acids / Q000737:chemistry; D002463:Cell Membrane Permeability; D002712:Chlorides / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D008567:Membranes, Artificial; D015394:Molecular Structure; D019158:N-Acetylneuraminic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism*; D000442:Octanols; D014867:Water
D001897:Boronic Acids; D002712:Chlorides; D008567:Membranes, Artificial; D000442:Octanols; D014867:Water; D019158:N-Acetylneuraminic Acid