The proposed research will involve the design of artificial restriction enzymes using the diferric complex of 1,3-di-(N,N-bis(2- benzimidazolymethyl)-amine)-2-hydroxyl propane (HPTB). Interest in synthesizing artificial restriction enzymes has been motivated by numerous possible applications in biological sciences and health sciences, particularly in the fields of molecular biology, structural biology, gene therapy, and pharmacology. Schnaith et al. recently demonstrated that Fe2(HPTB) can efficiently cleave DNA by hydrolysis, a reaction that has been difficult to catalyze. By linking Fe2(HPTB) to DNA intercalators or DNA binders, the resulting compounds should be able to specifically cleave DNA by hydrolysis. By linking Fe2(HPTB) to DNA binding proteins or long lengths of oligonucleotides, it should be possible to design compounds that can selectively cleave one fragment of DNA from a large genome so that another fragment can be inserted. Such compounds would be extremely valuable in treating genomic defects as well as a valuable tool in recombinant DNA technology.
