ENHANCED KIDNEY DIALYSIS MEMBRANES

Not Available Conducting Materials Corp. Proposes to support the antimalarial structure-based discovery efforts at Walter Reed Army Institure of Research, Division of Experimental Therapeutics. Specifically, serine hydroxymethyltransferase, an enzyme intimately linked to the metabolic functions of dihydrofolate reductase and thymidylate syntheses, will be targeted with a new generation of antimalarial agents. In Phase I, malarial SHMT will be cloned, sequenced, and expressed in bacteria. The functional enzyme will be purified for testing against potential antimalarial agents. The catalytic activity of the enzyme will be tested against some simple variation of substrates to get an approximation of the binding preferences of the malarial SHMT. At the same time, and RNA combinatorial library (SELEX) will be established to probe at and compare the active sites of host versus parasite metabolic enzymes. For proof of principle, the RNA combinatorial system will first be applied to drug-sensitive malarial DHFR since this protein is known to bind certain antifolate 1,000 times more tightly than the host enzyme. It is expected that the SELEX system will be able to identify RNA molecules that mimic the binding properties of drugs such as pyrimethamine. Phase II will design biased combinatorial libraries of small molecules.BENEFITS:Successful outcome of phase I&II will lead to anti-malarial drug development which will overcome the problem of drug resistant malarial parasites. Such