Design, Synthesis and Evaluation of Dipeptides as Probes for Studies of Gastrointestinal Tract Dipeptide Transport System

Abstract

The design of prodrugs suitable for transport by the dipeptide transporter can be a useful strategy for improving the absorption of small polar drugs which exhibit very poor bioavailability. A series of dipeptides (thirty two dipeptide compounds), in which the C-terminal residue is proline or a proline ester, has been synthesized. The inhibitory effect of these dipeptides on the uptake of the dipeptide Gly-Pro by a Caco-2 cell line has been determined by using tritium labeled substrates. The results suggest the dipeptide with proline benzyl ester and Glutamic acid benzyl ester has a good inhibitory activity.