A significant portion of the American and international economy depends on sucrose and its products. Although sucrose is the almost perfect sweetener and may provide for caloric intake, serious problems are associated with its use for human consumption. The most serious is dental caries, a bacterial disease causing widespread loss of productivity and deleterious to the nation's general health. Our research is designed to produce sucrose derivatives which may be capable of preventing oral disease. We plan to synthesize sucrose and other sugar derivatives which will inhibit glucan synthesis by streptococcal enzymes (glucosyltransferase, or GTF) which use sucrose as a substrate. Compounds, such as 3-keto-sucrose, 4-keto-sucrose, 6-aldehydo-sucrose, 6-aldehydo-methylglucoside and others will be synthesized and tested for their abilities to prevent glucan synthesis. Glucans are one of the virulence factors of the cariogenic streptococci and the inhibition of glucan synthesis may be a first step in the prevention of dental caries. The compounds which effectively inhibit glucan synthesis will be used to prevent acid production by the streptococci as well as to inhibit the adherence and accumulation of the bacteria onto saliva-coated surfaces. The genesis of dental caries depends on the sucrose-independent adherence of streptococci onto hydroxylapatite, then the glucan and sucrose-dependent accumulation of the pathogens and finally on acid production by the now localized organisms. Our approach to the design of anti-caries agents is to use a single compound to prevent adherence, accumulation and acid production. Such agents may ultimately provide a valuable means of preventing dental caries. Studies on the amino acid side chain reactivities of the streptococcal GTF(s) will be performed. In these studies a chemical reagent capable of selectively modifying a particular amino acid side chain will be used to probe the active site chemistry of the GTF(s). Modification reactions will be performed in the presence and absence of sucrose and other ligands of the enzyme(s). We hope to gain knowledge about the active site chemistry of the enzyme(s), thereby making it possible to design more effective inhibitors.
|Cox, S D; Lassiter, M O; Taylor, K G et al. (1994) Fluoride inhibits the glucan-binding lectin of Streptococcus sobrinus. FEMS Microbiol Lett 123:331-4|
|McAlister, D; Doyle, R J; Taylor, K G (1989) Inhibition by maltose, isomaltose, and nigerose of the synthesis of high-molecular-weight D-glucans by the D-glucosyltransferases of Streptococcus sobrinus. Carbohydr Res 187:131-8|
|Oakley, J D; Taylor, K G; Doyle, R J (1985) Trypsin-susceptible cell surface characteristics of Streptococcus sanguis. Can J Microbiol 31:1103-7|