Site-Specific Delivery and Activation of Drugs Using PhotoLabile Masks

Polina Kehayova and Prof. Ahamindra Jain
Swarthmore College
Summer 1998

Glaucoma is an eye disease whose symptoms are reduced by inhibition of Ocular Carbonic Anhydrase (CA). Since CA is present in every human cell, it is essential that an inhibitor be activated only after it is delivered to the specific site of its action. Some of the tightest binding inhibitors of CA are hydrophobic, which makes them hard to administer in the form of aqueous eye drops.

This summer Prof. Ahamindra Jain (one of my Chemistry professors :-)) and I are carrying out a project which is connected with developing a new approach for the site-specific delivery and activation of drugs using PhotoLabile Masks (PLMs). We plan to mask the activity of the hydrophobic inhibitor by attaching a hydrophilic PLM to it. Once the inhibitor is delivered to the specific site of its action, the PLM will be removed by irradiation with light, thus activating the inhibitor. The synthetic plan for the PLM-modified inhibitor that we are suggesting is shown in Scheme I.

The PLM is removed by breaking the Sulfur-Nitrogen bond after irradiation with light. The central part of the suggested PLM-modified inhibitor is what makes binding to the CA possible and the pentafluorobenzyl amide increases the binding energy. This summer we managed to synthesize the proposed compound and now it is left to demonstrate the principle of photocleavage.

Since we have made some exciting progress in this research, I would like to continue working on it during the school year. Probably future work on the project will include testing the system in vivo.