Development of Esterase Activated Prodrugs

A number of metalloproteins are associated with diseases ranging from heart disease to cancer, therefore by inhibiting their metal active site, one can control the catalysis of the protein. One must then find a kinetically efficient way of administering a pro-drug that is highly specific and strongly binding. To do this several esterase responsive protected metal binding groups are to be synthesized. Ester groups have emerged as an ideal protecting group, offering an improvement of the properties of small-molecule drugs. The ester group improves solubility, stability and bioavailability of drugs.  A series of the esterase responsive metal binding groups are to be protected with an acetyl group and another with a self-immolative linker. The cleavage of these protecting groups is to be activated by the addition of porcine liver esterase. Cleavage kinetics will be measured by UV-Vis spectroscopy. By obtaining the rate of the reaction, one will be able to determine which protecting group offers an efficient way of administering the drug.