This project continues and extends ongoing studies on the mechanism of synthesis of extracellular polysaccharides by cariogenic microorganisms. Earlier studies have established that periodate-treatment of soluble clinical dextran, an acceptor in the reactions catalyzed by several dextransucrases, results in the formation of a partially oxidised polysaccharide that is a potent and specific inhibitor of the dextransucrase activities. The proposed research program is directed towards elucidation of the mechanism of this inhibition and will include in vitro studies designed to assess the potential value of oxidized polysaccharides as therapeutic agents for modifying the plaque forming properties of Streptococcus mutans. The probable covalent attachment of inhibitor to enzyme will be confirmed by isolation and characterization of the inactive dextransucrase-oxidized dextran complex and a large number of potential inhibitors with different molecular sizes, linkage types and degrees of oxidation will be tested in order to define the structural requirement for a maximum inhibition of various dextransucrases. In addition several in vitro model systems will be used to test the effect of the dextransucrase inhibition on the aggregation and adherence to smooth surfaces of a selection of microorganisms. Although the greatest emphasis will be placed on studying the inhibition of dextransucrases, some time will be spent to establish whether other polysaccharide metabolising systems also may be subject to the same type of inhibition.