Abstract:
This thesis entails the design, synthesis, and DNA/Avidin binding properties of a platinum-biotin conjugate, which would serve as a "proof-of-concept" model for a new strategy for rational chemotherapy drug design. A compound was designed which would be able to simultaneously bind to DNA and the protein avidin. A two-step synthetic strategy was used to obtain the desired conjugate. First, reaction of N-hydroxysuccinimidobiotin with diethylenetriamine produced the diethylenetriaminobiotin intermediate 1. After purification, this intermediate was allowed to react with cis-bis(acetonitrile)dichloroplatinum (II) to produce the target compound, cis-diethlyenetriaminobiotinylchloro(acetonitrile)-platinull1 (II) chloride
2. Compound 2 was bound to DNA, whereupon agarose gel electrophoretic mobility shift assays showed that it did indeed recruit avidin binding to the nucleic acid.
It is thus shown that compounds can be designed to recruit preselected proteins to bind to DNA, even when the normal physiological function of that protein is unrelated to DNA binding. If a protein can be preselected which is specific to tumor cells, this strategy may have implications with regard to rational chemotherapy drug design.
