Phosphinic peptides have been widely used for the study of proteases so as to elucidate their function in health and disease by acting as reversible, non- toxic, potent and selective inhibitors of proteases. Some of the most interesting targets are Angiotensin Converting Enzyme (blood pressure regulation) and Matrix Metalloproteases (cancer). Nevertheless, the use of phosphinates as drugs presents a challenge with respect to their drug delivery. At physiological pH, phosphinates are negatively charged and, due to their polarity, are unable to penetrate cell membranes. To overcome this problem, esters can be used as prodrugs. These esters should meet several requirements, such as chemical stability / solubility of the prodrug in the gastrointestinal tract, good permeability across cell membranes, and finally efficient release of the drug at the target. Several kinds of such phosphinate esters have been developed, and have been used in clinical trials, but never sugar-based esters as proposed here. In this project the use of carbohydrates is examined and the results obtained so far are presented.
Moaz Abdou (Chemistry Department, XJTLU)