Microsporidia are obligate intracellular parasite characterized by a life cycle in which small unicellular spores are the means of transmission. They infect every major animal group, especially mammals, and are prominent pathogens in AIDS patients, in whom they can cause diarrhea, kertoconjunctivitis, hepatitis, urogenital infections, as well as respiratory and disseminated infections. The principal species include Enterocytozoon bienusi, Enc. hellum and Enc. cuniculi and their infections have no effective treatments. We found that Enc. cuniculi is very sensitive in vitro to analogs of the natural polyamines (spermine, spermidine and putrescine). One of them (BE-4-4-4-4) is a product of S LIL Pharmaceuticals, LLC (SL-11061) and is also very active against Enc. hellum and Enc. Intestinalis. S LIL Pharmaceuticals will therefore develop a series of polyamine analogs designed to affect the conformations and strand distances of DNA and tRNA of microsporidia in order to inhibit their proliferation. The new polyamines will be analogs of bisethyl spermine (BE-3-4-3) with conformationally restricted residues that will confer to them partially rigid structures. Pairs of helical and stretched conformers of the new polyamines will confer regiospecificity to their binding to nucleic acids and predictably interfere with protein synthesis and cell growth of microsporidia. PROPOSED COMMERCIAL APPLICATION Synthesis of polyamine analogs inhibitors of the growth of microsporidia, parasites that infect every major animal group, especially mammals, and are prominent pathogens in AIDS patients. The new polyamine analogs represent a new type of antiproliferative drug with promising antiparasitic activities. These studies will be a prelude to phase II studies with selected compounds that will be tested in vivo in athymic mice with microsporidiosis.