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 Citations (Scopus)

Abstract

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
Volume18
Issue number1
DOIs
StatePublished - Jan 11 2016

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Proteins
Peptides
Modulators

Keywords

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

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Converting One-Face α-Helix Mimetics into Amphiphilic α-Helix Mimetics as Potent Inhibitors of Protein-Protein Interactions. / Lee, Ji Hoon; Oh, Misook; Kim, Hyun Soo; Lee, Huisun; Im, Wonpil; Lim, Hyun-Suk.

In: ACS Combinatorial Science, Vol. 18, No. 1, 11.01.2016, p. 36-42.

Research output: Contribution to journalArticle

Lee, Ji Hoon ; Oh, Misook ; Kim, Hyun Soo ; Lee, Huisun ; Im, Wonpil ; Lim, Hyun-Suk. / Converting One-Face α-Helix Mimetics into Amphiphilic α-Helix Mimetics as Potent Inhibitors of Protein-Protein Interactions. In: ACS Combinatorial Science. 2016 ; Vol. 18, No. 1. pp. 36-42.
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