Converting One-Face α-Helix Mimetics into Amphiphilic α-Helix Mimetics as Potent Inhibitors of Protein-Protein Interactions

Ji Hoon Lee, Misook Oh, Hyun Soo Kim, Huisun Lee, Wonpil Im, Hyun-Suk Lim

Research output: Contribution to journalArticle

8 Scopus citations


Many biologically active α-helical peptides adopt amphiphilic helical structures that contain hydrophobic residues on one side and hydrophilic residues on the other side. Therefore, α-helix mimetics capable of mimicking such amphiphilic helical peptides should possess higher binding affinity and specificity to target proteins. Here we describe an efficient method for generating amphiphilic α-helix mimetics. One-face α-helix mimetics having hydrophobic side chains on one side was readily converted into amphiphilic α-helix mimetics by introducing appropriate charged residues on the opposite side. We also demonstrate that such two-face amphiphilic α-helix mimetics indeed show remarkably improved binding affinity to a target protein, compared to one-face hydrophobic α-helix mimetics. We believe that generating a large combinatorial library of these amphiphilic α-helix mimetics can be valuable for rapid discovery of highly potent and specific modulators of protein-protein interactions.

Original languageEnglish (US)
Pages (from-to)36-42
Number of pages7
JournalACS Combinatorial Science
Issue number1
StatePublished - Jan 11 2016



  • amphiphilic α-helix mimetics
  • combinatorial library
  • protein-protein interaction inhibitor
  • solid-phase synthesis

ASJC Scopus subject areas

  • Chemistry(all)

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