Pharmacological characterization of novel marine toxins

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DESCRIPTIO,N (provided by applicant): Natural source compounds have been critical for the elucidation of glutamate receptor (GluR) function and classification. Excitatory amino acids derived from the manne sponges, such as dysiderbaine (DH), have proven to be valuable tools for characterizing GluRs. This project will determine the pharmacological profile of neoDH (a natural analog of DH) and MSVIII-19 (an intermediate of DH synthesis) on glutamate receptors. Preliminary experiments show, analogues of DH activate kainite receptors selectively and antagonize KA and AMPA receptors (neoDH and MSVIII-19, respectively). Further characterization of the marine toxins will involve testing the compounds on an array of receptors including both ionotropic and metabotropic GluRs. Pharmacological profiling of these compounds is critical to determine the structural components that confer GluR specificity in tandem, homology modeling of KAR subunits with DH and the analogs bound will be utilized to determine the amino acid residues critical for the binding and selectivity of the toxins. The characterization of these compounds will facilitate future modification in design and synthesis of selective GluR compounds.