The discovery of the physiological role of a great number of peptides (e.g. angiotensin II, neuropeptide Y, enkephalin, gonadotrophin-releasing hormone…) stimulated researchers towards design and synthesis of analogues. Since the last two decades, peptidomimetics have emerged as promising therapeutic agents such as goserelin, cetrorelix, and atazanavir. Structural modifications of the sequence of the native peptides can optimize their biological properties such as bioavailibilty, plasma half-life, resistance of metabolism and selectivity. Another advantage to develop peptidomimetics as drugs and/or probes can be the control of their conformation. A peptidomimetic with a restricted conformational flexibility can minimize binding to non-target receptors and then enhances the activity at the target receptor or transporter. Taking all together, peptidomimetics constitute a class of promising biomolecules to study ligand-protein interactions on different biological targets.

For many years, our researchers worked on multidrug resistance (MDR) to anticancer and anti-infectious agents. This phenomenon is often associated with over-expression of several proteins belonging to ABC transporters (e.g. ABCB1, ABCG2). Numerous molecules have shown activities on these transporters. Among them, we can list steroids, bivalent ligands, azaheterocycles and short linear hydrophobic peptides. For example, reversin 121, a dipeptide, showed high affinity and specificity for ABCB1.

Reversin 121 became the new starting point of our research. For 2005 we developed different series of (aza)peptidomimetic-type ligands of ABC transporters. First, we wish to expose on the synthesis work accomplished to reach our selection of molecules and secondly to present our biological data on ABCB1, and ABCG2.