Back to overview

A mixed chirality α-helix in a stapled bicyclic and a linear antimicrobial peptide revealed by X-ray crystallography

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Baeriswyl Stéphane, Personne Hippolyte, Di Bonaventura Ivan, Köhler Thilo, van Delden Christian, Stocker Achim, Javor Sacha, Reymond Jean-Louis,
Project Chemical Space Design of Small Molecules and Peptides
Show all

Original article (peer-reviewed)

Journal RSC Chemical Biology
Volume (Issue) 2(6)
Page(s) 1608 - 1617
Title of proceedings RSC Chemical Biology
DOI 10.1039/d1cb00124h

Open Access

Type of Open Access Publisher (Gold Open Access)


The peptide α-helix is right-handed when containing amino acids with L-chirality, and left-handed with D-chirality, however mixed chirality peptides generally do not form α-helices unless a helix inducer such as the non-natural residue amino-isobutyric acid is used. Herein we report the first X-ray crystal structures of mixed chirality α-helices in short peptides comprising only natural residues as the example of a stapled bicyclic and a linear membrane disruptive amphiphilic antimicrobial peptide (AMP) containing seven L- and four D-residues, as complexes of fucosylated analogs with the bacterial lectin LecB. The mixed chirality α-helices are superimposable onto the homochiral α-helices and form under similar conditions as shown by CD spectra and MD simulations but non-hemolytic and resistant to proteolysis. The observation of a mixed chirality α-helix with only natural residues in the protein environment of LecB suggests a vast unexplored territory of α-helical mixed chirality sequences and their possible use for optimizing bioactive α-helical peptides.