FIGURE 1.

Roadmap for peptidomimetics design. Starting from the native peptide (1), first step regards establishing the shortest peptide fragment with activity, as well as identification of key residues involved in recognition (in red) (2). Next, using information about the secondary structure of the peptide in its bound conformation, proceed to design conformationally constrained analogs mimicking the bioactive conformation (3). These analogs represent the first generation peptidomimetics. Finally, identification of small molecule scaffolds that permit a correct spatial arrangement of relevant chemical groups (identified in step 2) to yield second generation peptidomimetics (4).