A modular approach for organizing dimeric coiled coils on peptoid oligomer scaffolds

Linhai Jiang, Kent Kirshenbaum

Research output: Contribution to journalArticle

Abstract

We report a general approach to promote the folding of synthetic oligopeptides capable of forming homodimeric coiled coil assemblies. By pre-organizing the peptides on macrocyclic oligomer scaffolds, the stability of the coiled coils is enhanced with an observed increase in the melting temperature of 30 °C to 40 °C. Molecular dynamics simulations substantiate the hypothesis that the enhanced stability is established by constraining motion at the peptide termini and by pre-organizing intramolecular helix-helix contacts. We demonstrate the modularity of this approach by using a family of peptoid scaffolds to promote the folding of a dimeric coiled coil. Importantly, this strategy for templating coiled coils allows preservation of native amino acid sequences. Comparing a macrocyclic peptoid scaffold to its linear counterparts indicates that both types of assemblies are effective for organizing stable coiled coils. These results will guide future designs of coiled coil peptides for biomedical applications and as building blocks for more complex supramolecular assemblies.

Original languageEnglish (US)
Pages (from-to)2312-2320
Number of pages9
JournalOrganic and Biomolecular Chemistry
Volume18
Issue number12
DOIs
StatePublished - Mar 28 2020

ASJC Scopus subject areas

  • Biochemistry
  • Physical and Theoretical Chemistry
  • Organic Chemistry

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