Figure 1.

Peptidomimetics design roadmap. Starting from the native peptide sequence (1) when the 3D structure of the peptide/receptor complex is not known, first step regards the synthesis of linear analogs (2) to establish the shortest peptide fragment with activity and to identify key residues for receptor recognition (in red). Next step consists of designing conformationally constrained analogs (3), using information about the secondary structure of the peptide in its bound conformation. The final step is the identification of small molecule scaffolds (4) that permit a correct spatial arrangement of relevant chemical groups. Knowledge of the peptide/receptor 3D structure permits to undertake a shortcut.