Quantitative Detection of Toxins Using Novel Compounds that Bind to Carbonhydrate Binding Sites

A novel set of compounds has been devised and synthesized, members of which bind to bacterial toxins with high affinity and selectivity. The compounds are covalently attached to a solid phase and can be used to selectively bind to toxins from various sources (e.g., body fluids or food extracts) for their detection and quantitation. In this proposal is described the theoretical background for the construction and nature of the compounds, and their selective binding with the ricin agglutinin, the botulinum toxin A hemagglutinin component, and the botulinum A, B, and E neurotoxin components. Data is presented that compounds can be obtained that will be selective for a host of other pathogenic toxins. Using these toxin selective binding compounds, ELISA and other detection-quantitation assays will be developed for the ricin and botulinum toxins. The sensitivities, reproducibilities, and applications of the assays will be tested by addition of purified toxins to serum/plasma and to selected foods, and the conduct of quantitative assay. Because of the nature of the compounds binding to the toxins, it is expected that the compounds may also be used therapeutically to inhibit the toxin effects. In Phase II, compounds that bind selectively to a number of additional toxins will be identified and quantitative assays constructed. The assays would be used to quantify toxin levels in appropriate clinical situations and in the field. BENEFITS: The toxin-binding compounds are stable and assay tests can be constructed that can be stored at typical room temperatures and which would withstand higher temperatures that may be experienced in shipping or in the field. Thus, the assays could be used in a number of situations including medical and veterinary applications, as well as in the food industry. The toxin binding compounds may also be used to inhibit toxin binding and thus neutralize the potential harmful physiological effects of the toxins.