Hybrid Peptides Based on α‐Aminoxy Acids as Antimicrobial and Anticancer Foldamers

Abstract

α-Aminoxy peptides represent an interesting group of peptidomimetics with high proteolytic stability and the ability to fold into specific, predictable secondary structures. Here, we present a series of hybrid peptides consisting of α-aminoxy acids and αamino acids with cationic and aromatic, hydrophobic side chains in an alternating manner synthesized using an efficient protocol that combines solution-and solid-phase synthesis. 2D ROESY experiments with a representative hexamer suggested the presence of a 7/8 helical conformation in solution. Biological evaluation revealed a significant impact of the peptide chain length and the N-terminal cap on the antimicrobial and anticancer properties of this series of hybrid peptides. The Fmoc-capped peptide 6e displayed the most potent antimicrobial activity against a panel of Gram-negative and Gram-positive bacterial strains (e. g. against E.

Advances in hybrid peptide-based self-assembly systems and their applications

“…These hybrid peptides also showed improved stability against trypsin. 133 The importance of substitution with an unnatural counterpart in biological activity was also shown by Demizu and his group. They identified antimicrobial peptides Magainin 2 (Mag 2: H-GIGKFLHSAKKFGKAFVGEIMNS-NH 2 ), present in frog skin, and synthesized truncated peptides derived from Mag 2.…”

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

“…(Figure 1). In the same class, δ-and ε-peptides, aza-β 3 -peptides, pyrrolinones, α-aminooxy-peptides and sugar-based peptides have been reported as foldamers and have been investigated for the development of bioactive peptides [2,[26][27][28][29][30]. Moreover, the side-chain stapling of the peptides has been widely used to stabilize their helical structure, and many PPI inhibitors based on stapled peptides have been reported [31].…”