The proposed research is to elucidate the chemistry and biosynthesis of algal and other aquatic toxins which have serious impact on public health. The chemical work is intended to provide basic information to design preventive and curative measures, and also to discover new site-specific toxins as tools to investigate important biological mechanisms involving neural receptors such as sodium channels and glutamate receptors. The biosynthesis work is intended to elucidate the sites of formation and unique metabolic pathways in aquatic organisms. The resulting information will help to consider such important issues as the virulency acquisition of red tide organisms and marine animals, and the mass production of important marine products. Specifically, the structures, distribution, and biosynthesis of 1) excitatory amino acids such as domoic acid and kainic acid; 2) paralytic shellfish poisons (PSP) such as saxitoxin and gonyautoxins; 3) polyether toxins such as brevetoxins and okadaic acid derivatives; 4) blue-green algal toxins such as cyanoginosins and aphanorphin; 5) tetrodotoxin and its derivatives will be investigated. The work will involve the culturing of organisms, analysis and purification of toxins using chromatographic methods, structure elucidation by modern spectroscopic methods such as 2D-NMR and X-ray crystallography, and isotope labeling studies using both stable and radioactive isotopes. Isolated toxins will be provided to neurophysiologists for pharmacological studies.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37GM028754-17
Application #
3484650
Study Section
Bio-Organic and Natural Products Chemistry Study Section (BNP)
Project Start
1980-09-01
Project End
1995-06-30
Budget Start
1992-07-01
Budget End
1993-06-30
Support Year
17
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Rhode Island
Department
Type
Schools of Pharmacy
DUNS #
135531015
City
Kingston
State
RI
Country
United States
Zip Code
02881
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Konishi, Masataka; Yang, Xuemin; Li, Bo et al. (2004) Highly cytotoxic metabolites from the culture supernatant of the temperate dinoflagellate Protoceratium cf. reticulatum. J Nat Prod 67:1309-13
Shimizu, Yuzuru (2003) Microalgal metabolites. Curr Opin Microbiol 6:236-43
Levine, L; Shimizu, Y (1992) Antibodies to brevetoxin B: serologic differentiation of brevetoxin B and brevetoxin A. Toxicon 30:411-8
Shimizu, Y (1986) Chemistry and biochemistry of saxitoxin analogues and tetrodotoxin. Ann N Y Acad Sci 479:24-31