Design and Synthesis of Crosslinked Helix Dimers as Protein Tertiary Structure Mimics

Seong Ho Hong, Thu Nguyen, Paramjit Arora

Research output: Contribution to journalArticlepeer-review


Crosslinked helix dimers (CHDs) are synthetic tertiary helical structure motifs designed to modulate interactions of proteins with binding partners. Helix dimers serve as mimics of coiled coils, which are known to be implicated in a multitude of protein complexes. Coiled coils are typically stable in long peptides (>21-28 residues), because sufficient intra- and interstrand contacts are not available in short peptides to coax strand assembly. To engineer conformationally stable CHDs in short sequences, we introduced a covalent linkage in place of an interhelical salt bridge and sculpted the helical interface with optimal hydrophobic packing. CHDs have shown efficacy for the disruption of targeted protein-protein interactions in biochemical, cellular, and animal models. This article describes our optimized approach to design and synthesize parallel and antiparallel helical tertiary structure mimics. Synthesis of CHDs involves conjugation of individual peptide segments, purification of the mono-conjugated strand, and alkylation of the two independent strands to yield crosslinked dimers.

Original languageEnglish (US)
Article numbere315
JournalCurrent Protocols
Issue number1
StatePublished - Jan 2022


  • Amino Acid Sequence
  • Peptides
  • Protein Binding
  • Protein Domains
  • Proteins

ASJC Scopus subject areas

  • Medical Laboratory Technology
  • General Medicine
  • General Biochemistry, Genetics and Molecular Biology
  • General Immunology and Microbiology
  • Health Informatics
  • General Neuroscience
  • Pharmacology, Toxicology and Pharmaceutics(all)


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