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Hybrid Peptides Based on α‐Aminoxy Acids as Antimicrobial and Anticancer Foldamers
Author(s) -
Sinatra Laura,
Kolano Lisa,
Icker Maik,
Fritzsche Stefan R.,
Volke Daniela,
Gockel Ines,
Thieme René,
Hoffmann Ralf,
Hansen Finn K.
Publication year - 2021
Publication title -
chempluschem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.801
H-Index - 61
ISSN - 2192-6506
DOI - 10.1002/cplu.202000812
Subject(s) - random hexamer , chemistry , peptide , antimicrobial , peptidomimetic , antimicrobial peptides , combinatorial chemistry , cationic polymerization , amino acid , solid phase synthesis , stereochemistry , cyclic peptide , biochemistry , organic chemistry
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 α‐amino 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. Coli : MIC=8 mg/L; S. aureus : MIC=4 mg/L).