Phage Selection of Chemically Stabilized α-Helical Peptide Ligands.

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Serval ID
serval:BIB_0A65DEA92978
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Phage Selection of Chemically Stabilized α-Helical Peptide Ligands.
Journal
ACS chemical biology
Author(s)
Diderich P., Bertoldo D., Dessen P., Khan M.M., Pizzitola I., Held W., Huelsken J., Heinis C.
ISSN
1554-8937 (Electronic)
ISSN-L
1554-8929
Publication state
Published
Issued date
20/03/2016
Peer-reviewed
Oui
Volume
11
Number
5
Pages
1422-1427
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Comment
Publication Status: ppublish
Abstract
Short α-helical peptides stabilized by linkages between constituent amino acids offer an attractive format for ligand development. In recent years, a range of excellent ligands based on stabilized α-helices were generated by rational design using α-helical peptides of natural proteins as templates. Herein, we developed a method to engineer chemically stabilized α-helical ligands in a combinatorial fashion. In brief, peptides containing cysteines in position i and i + 4 are genetically encoded by phage display, the cysteines are modified with chemical bridges to impose α-helical conformations, and binders are isolated by affinity selection. We applied the strategy to affinity mature an α-helical peptide binding β-catenin. We succeeded in developing ligands with Kd's as low as 5.2 nM, having >200-fold improved affinity. The strategy is generally applicable for affinity maturation of any α-helical peptide. Compared to hydrocarbon stapled peptides, the herein evolved thioether-bridged peptide ligands can be synthesized more easily, as no unnatural amino acids are required and the cyclization reaction is more efficient and yields no stereoisomers. A further advantage of the thioether-bridged peptide ligands is that they can be expressed recombinantly as fusion proteins.
Keywords
Amino Acid Sequence, Bacteriophages/metabolism, Ligands, Molecular Conformation, Molecular Sequence Data, Peptide Library, Peptides/chemistry, beta Catenin/metabolism
Pubmed
Create date
26/06/2016 16:09
Last modification date
07/04/2021 6:34
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