From Peptides to Non‐Peptide Alpha‐Helix Inducers and Mimetics

Helix mimetics are good models for investigating the theories of protein folding and also act as good affinity ligands for therapeutic applications due to their biostability and better blood‐brain barrier crossing ability. The helix mimetics display the same spatial and temporal orientation with respect to the amino acid side‐chains of alpha helix part of the protein, which are involved in protein–protein interactions. The designed nonpeptidic molecules with substituents at the appropriate positions on the scaffold can mimic the amino acid side‐chains of a fully folded alpha helix and can competitively bind with the target protein, thus acting as possible therapeutic agents. This was illustrated with examples like p53/MDM2, CD81/CV E2, Bcl‐x L /Bak, gp‐41, and others, with therapeutic relevance. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)