β- and γ-amino acids at α-helical interfaces: Toward the formation of highly stable foldameric coiled coils

Elisabeth K. Nyakatura, Jérémie Mortier, Vanessa S. Radtke, Sebastian Wieczorek, Raheleh Rezaei Araghi, Carsten Baldauf, Gerhard Wolber, Beate Koksch

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Since peptides are vital for cellular and pathogenic processes, much effort has been put into the design of unnatural oligomers that mimic natural peptide structures, also referred to as foldamers. However, to enable the specific application of foldamers, a thorough characterization of their interaction profiles in native protein environments is required. We report here the application of phage display for the identification of suitable helical environments for a sequence comprising an alternating set of β- and γ-amino acids. In vitro selected sequences show that an increase in the hydrophobic surface area at the helical interface as well as the incorporation of a polar H-bond donor functionality can significantly improve interhelical interactions involving backbone-extended amino acids. Thus, our data provide insight into the principles of the rational design of foldameric inhibitors for protein-protein interactions.

Original languageEnglish (US)
Pages (from-to)1300-1303
Number of pages4
JournalACS Medicinal Chemistry Letters
Volume5
Issue number12
DOIs
StatePublished - Dec 11 2014
Externally publishedYes

Keywords

  • Phage display
  • chimeric peptides
  • βγ amino acids

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

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    Nyakatura, E. K., Mortier, J., Radtke, V. S., Wieczorek, S., Rezaei Araghi, R., Baldauf, C., Wolber, G., & Koksch, B. (2014). β- and γ-amino acids at α-helical interfaces: Toward the formation of highly stable foldameric coiled coils. ACS Medicinal Chemistry Letters, 5(12), 1300-1303. https://doi.org/10.1021/ml500361c