An Effective Strategy for Stabilizing Minimal Coiled Coil Mimetics

Michael G. Wuo, Andrew B. Mahon, Paramjit Arora

Research output: Contribution to journalArticle

Abstract

Coiled coils are a major motif in proteins and orchestrate multimerization of various complexes important for biological processes. Inhibition of coiled coil-mediated interactions has significant biomedical potential. However, general approaches that afford short peptides with defined coiled coil conformation remain elusive. We evaluated several strategies to stabilize minimal helical bundles, with the dimer motif as the initial focus. A stable dimeric scaffold was realized in a synthetic sequence by replacing an interhelical ionic bond with a covalent bond. Application of this strategy to a more challenging native protein-protein interaction (PPI) suggested that an additional constraint, a disulfide bond at the internal a/d′ position along with a linker at the e/e′ position, is required for enhanced conformational stability. We anticipate the coiled coil stabilization methodology described herein to yield new classes of modulators for PPIs.

Original languageEnglish (US)
Pages (from-to)11618-11621
Number of pages4
JournalJournal of the American Chemical Society
Volume137
Issue number36
DOIs
StatePublished - Sep 16 2015

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Protein Multimerization
Proteins
Biological Phenomena
Disulfides
Covalent bonds
Scaffolds
Dimers
Peptides
Modulators
Conformations
Stabilization

ASJC Scopus subject areas

  • Chemistry(all)
  • Catalysis
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

An Effective Strategy for Stabilizing Minimal Coiled Coil Mimetics. / Wuo, Michael G.; Mahon, Andrew B.; Arora, Paramjit.

In: Journal of the American Chemical Society, Vol. 137, No. 36, 16.09.2015, p. 11618-11621.

Research output: Contribution to journalArticle

Wuo, Michael G. ; Mahon, Andrew B. ; Arora, Paramjit. / An Effective Strategy for Stabilizing Minimal Coiled Coil Mimetics. In: Journal of the American Chemical Society. 2015 ; Vol. 137, No. 36. pp. 11618-11621.
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