Reactivity of Carbohydrate Phosphodiesters, Potential Targets of Antibacterial Agents

Abstract

While monosaccharide units in bacterial carbohydrates may be linked with phosphodiester bonds, human carbohydrates exclusively contain glycosidic linkages. Differences between human and bacterial carbohydrates present potential targets for the development of novel antibacterial agents. The purpose of the present article is to study the reactivity of carbohydrate phosphodiester models to evaluate the possibility of a selective inactivation of bacterial carbohydrates within a biological matrix. The model compound was chosen for the ease of synthesis and the convenience of detection. Its reactivity was studied in the presence and in the absence of metal ion-based catalysts. The results obtained show that the spontaneous reaction under neutral conditions is the glycoside hydrolysis, but metal catalysts enhance the cleavage by intramolecular transesterification. The reactivity was lower than that of the phosphodiester bonds of RNA under the same conditions. Corresponding phosphorothioates were synthesized to study the effect of the coordination of metal ion catalysts. However, unexpected reactions were observed, and in addition to glycoside hydrolysis, phosphorothioates reacted similarly to corresponding RNA analogs, resulting in the cleavage, phosphate migration, and desulphurization. Different metal ion catalysts steered the reaction in different directions.