PPII Helical Peptidomimetics Templated by Cation–π Interactions

Timothy W. Craven, Richard Bonneau, Kent Kirshenbaum

Research output: Contribution to journalArticle

Abstract

Poly-proline type II (PPII) helical PXXP motifs are the recognition elements for a variety of protein–protein interactions that are critical for cellular signaling. Despite development of protocols for locking peptides into α-helical and β-strand conformations, there remains a lack of analogous methods for generating mimics of PPII helical structures. We describe herein a strategy to enforce PPII helical secondary structure in the 19-residue TrpPlexus miniature protein. Through sequence variation, we showed that a network of cation–π interactions could drive the formation of PPII helical conformations for both peptide and N-substituted glycine peptoid residues. The achievement of chemically diverse PPII helical scaffolds provides a new route towards discovering peptidomimetic inhibitors of protein–protein interactions mediated by PXXP motifs.

Original languageEnglish (US)
Pages (from-to)1824-1828
Number of pages5
JournalChemBioChem
DOIs
StatePublished - Oct 4 2016

Fingerprint

Peptidomimetics
Proline
Cations
N-substituted Glycines
Conformations
Peptoids
Cell signaling
Peptides
Scaffolds
Proteins

Keywords

  • foldamers
  • miniature protein design
  • peptoids
  • PPII helices
  • PXXP motif mimetics

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Organic Chemistry

Cite this

PPII Helical Peptidomimetics Templated by Cation–π Interactions. / Craven, Timothy W.; Bonneau, Richard; Kirshenbaum, Kent.

In: ChemBioChem, 04.10.2016, p. 1824-1828.

Research output: Contribution to journalArticle

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