Evolution in non-peptide α-helix mimetics on the road to effective protein-protein interaction modulators.

摘要: Modulation of interactome networks, essentially protein-protein interactions (PPIs), might represent valuable therapeutic approaches to different pathological conditions. Since a high percentage PPIs are mediated by α-helical structures at the interacting surface, development compounds able reproduce amino acid side-chain organization α-helices (e.g. stabilized α-helix peptides and β-derivatives, proteomimetics, small-molecule mimetics) focuses attention research groups. This appraisal describes recent progress in non-peptide mimetics field, which has evolved from single-face multi-face reproducing oligomeric monomeric scaffolds bear substituents similar spatial dispositions as side-chains canonical helices. Grouped chemical structures, review contemplates terphenyl-like molecules, oligobenzamides heterocyclic analogues, benzamide-amino conjugates non-oligomeric small-molecules mimetics, among others, their effectiveness stabilize/disrupt therapeutically relevant PPIs. The X-ray couple peptidomimetics some complexed with MDM2 protein, well state art on clinical trials, also remarked. discovery continuously increasing number new disease-relevant could offer future opportunities for these other forthcoming mimetics.