Design, Synthesis and Evaluation of Dipeptides as Probes for Studies of Gastro-Intestinal Tract Dipeptide Transport

Abstract

The use of peptides and proteins as drugs is limited in part by their poor absorption by the gastro-intestinal tract. A knowledge of the mechanics by which this absorption occurs may lead to the design of more effective peptide-based drugs, and work presented here is an initial study into the relationship between simple peptides and their uptake. A series of dipeptides, in which the C-terminal residue is proline or a proline ester, has been synthesised. The inhibitory effect of these dipeptides on the uptake of the dipeptide Gly-Pro by a Caco-2 (the human colorectal carcinoma cell line) cell line has been determined by using tritium labelled substrates. Structural features, which lead to increase the inhibitory potency with various series of inhibitor synthesis were identified.