Figure 1. Primary amines used in the synthesis of the library of peptoids.

Scheme 1. Solid-phase synthesis of the library of peptoids.

Figure 2. Screening of the library of N-alkylglycine trimers for multidrug resistance (MDR) reversal agents. The individual bars in the panels represent the relative percentage of intracellular daunomycin (DNM) accumulation for each peptoid mixture, with the x-axis representing the defined amine (‘O’ position), for the three separate positional sublibraries: OXX, XOX and XXO. The results at 0.1 mg/mL. Striped bars indicate the mixtures selected for the identification of individual peptoids. Mixtures were selected for deconvolution according to their activity and cytotoxicity. Values for DNM (3 mM) are also indicated for each bar panel.

Figure 3. Relative percentage of intracellular daunomycin (DNM) accumulation of individual peptoids at 5 μM in the P-glycoprotein overexpressing, murine leukaemic resistant cell line L1210R. Values for DNM (3 μM) and verapamil (VRP, 5 μM) are also given.

Figure 4. Structures of the peptoid hits identified in the present study.

Figure 5. (Left) Peptoid 2 fit into the pharmacophore model generated by Catalyst. The pharmacophore is composed of two hydrophobic regions (cyan), one aromatic ring (orange) and two hydrogen bond acceptors (green). One of the hydrogen bond acceptors, which did not interact with peptoid 2, has been removed for clarity. (Right) Verapamil fit into the same pharmacophore for comparison purposes.