Host-rotaxane as cellular transport agents with an enzymatic switch

ORGN 611

Jennifer H. Lunn, lunnjh@email.uc.edu and David B Smithrud. Department of Chemistry, University of Cincinnati, 2600 Clifton Ave., Cincinnati, OH 45221
The binding domain of an antibody is a paradigm for the development of a synthetic host. Host-rotaxanes combine recognition elements in a similar convergent arrangement as found with antibodies. Besides forming tight complexes with various guests, host-rotaxanes are highly efficient cellular transport agents. The rotaxane operates through a passive transport mechanism, so there is no control over what cell it enters. We are currently constructing host-rotaxanes with an "on" switch to obtain cell-selectivity. Highly charged peptides will be added to the transporters, which should make them impermeable. Enzymatic cleavage of these peptides will turn the transporter on and it will enter cells. The long-term goal is to create transporters that are turned on by enzymes that are over expressed at tumor sites. These transporters will become part of a new anti-cancer therapy.