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Publication Abstract from PubMed

The peptide alpha-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 alpha-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 alpha-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 alpha-helices are superimposable onto the homochiral alpha-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 alpha-helix with only natural residues in the protein environment of LecB suggests a vast unexplored territory of alpha-helical mixed chirality sequences and their possible use for optimizing bioactive alpha-helical peptides.

A mixed chirality alpha-helix in a stapled bicyclic and a linear antimicrobial peptide revealed by X-ray crystallography.,Baeriswyl S, Personne H, Di Bonaventura I, Kohler T, van Delden C, Stocker A, Javor S, Reymond JL RSC Chem Biol. 2021 Aug 20;2(6):1608-1617. doi: 10.1039/d1cb00124h. eCollection, 2021 Dec 2. PMID:34977576^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.