Binding of aminoglycoside antibiotics to acidic mucopolysaccharides.

Abstract

Binding of aminoglycoside antibiotics to acidic mucopolysaccharides was studied by means of physicochemical methods. Reactivity was affected markedly by the ionic environment, e.g., pH and ionic strength of the medium, the concentrations and the molar ratios of the constituents. The ionic character of binding was further confirmed by gel chromatography. The reduction of metachromasis by an aminoglycoside was also observed. Their affinity is correlated with localization of the aminoglycosides in vivo. According to reactivity, the following descending order of affinity was obtained for each family: neomycin, gentamicin, sagamicin, kanamycin and streptomycin; heparin, chondroitin sulfate and hyaluronic acid. This sequence of aminoglycosides corresponds to the extent of oto-, nephro- and neuro-(acute)toxicity, suggesting that their affinity for acidic mucopolysaccharides contribute to their tissue toxicity.