BIOACTIVE COMPOUNDS AND MEMBRANE PROTEINS

Ascidians, sessile chordates which inhabit all of the oceans display a remarkable ability to sequester and reduce vanadium in blood cells (concentrations up to 1M, or up to 107 times that of sea-water). However, the function of this bioinorganic process has remained an enigma since the last century. A physiological role for vanadium in animals remains conspicuously absent, although it is considered to be an essential trace element. The isolation and characterization of the first member of tunichromes, a new class of blood pigments showed it to be a metal complexing/reducing hydroquinonoid compound; its total synthesis has now been completed. The goal is to clarify its inferred role in vanadium assimilation, and the unknown biological roles of tunichromes and vanadium; this should also contribute to our understanding of the unknown role of vanadium in mammalians. Calcium ions play a number of roles in various cells. In nerve cells, calcium influx, regulated by voltage- independent calcium channel, triggers the release of neurotransmitters. While different calcium channel blockers have been described in past years, a true blocker for the main calcium-dependent action potential in mammalian and in some molluscan neurons had not been encountered. However, such a blocker has recently been found to be present in the venom of American funnel-web spider; the full characterization of this toxin is proposed. Although the receptor proteins of glutamate, prostaglandins, and ecdysone (insect molting hormone) have attracted great interest and many groups are engaged in their isolation and characterization (of the genes and proteins) the goals have not yet been achieved. It is proposed that these objectives will be pursued by using the techniques of photoaffinity labeling and/or affinity chromatography. The glutamate receptor study is based on a potent antagonist isolated from the venom of an African wasp, while the ecdysone project is based on a potent ecdysone analog. The prostaglandin receptors will be studied by introducing photoaffinity labels into readily available prostaglandins by a general route, and use these as probes for searching for the respective receptors.