Helical Foldamers and Stapled Peptides as New Modalities in Drug Discovery: Modulators of Protein-Protein Interactions

Abstract

A “foldamer” is an artificial oligomeric molecule with a regular secondary or tertiary structure consisting of various building blocks. A “stapled peptide” is a peptide with stabilized secondary structures, in particular, helical structures by intramolecular covalent side-chain cross-linking. Helical foldamers and stapled peptides are potential drug candidates that can target protein-protein interactions because they enable multipoint molecular recognition, which is difficult to achieve with low-molecular-weight compounds. This mini-review describes a variety of peptide-based foldamers and stapled peptides with a view to their applications in drug discovery, including our recent progress.

Unnatural helical peptidic foldamers as protein segment mimics

“…111 As mimics of natural helical proteins, unnatural helical peptidic foldamers have richer chemical diversity, increased enzymatic stability and chemical availability, which make them potential drug candidates. 112,113 Here, we present some representative examples of the use of unnatural helical peptidic foldamers to modulate disease-related PPIs over the past decade.…”

Synthesis of macrocyclization cyclophanes and their metal complexes, characterization and antimicrobial activity

“…The antimicrobial activities of these compounds were measured in Tryptic Soy Broth standards (TSB) at 37°C for 24 h. Viability values at 600 nm were measured by comparing 24 and 48-h for the incubation period. The Clinical laboratory standards institute was conducted for antimicrobial tests [20].…”

Herringbone Helical Foldamers from Aromatic Ether Derived ϵ‐Amino Acid Peptides

“…Famous examples include Lehn's oligo(pyridine), [26] Jiang and Huc's quinoline‐derived δ ‐peptide, [25b,27] Chen's phenanthroline dicarboxamide based helical foldamer, [28] Gong's crescent oligoamides, [29] Li's oligohydrazides, [30] Gellman's ortho ‐terphenyl amino acid based oligomers, [31] aromatic and aliphatic hybrid backbone based on 2‐(2‐aminophenoxy)acetic acid, [32] etc. On the basis of structure investigations, wide applications of foldamers in catalysis, [33] drug discovery, [34] mimicking of tertiary and/or quaternary structures of biopolymers, [35] circularly polarized luminescence, [36] etc., have also been explored.…”