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

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• 作者：Ji Hoon Lee ; Misook Oh ; Hyun Soo Kim ; Huisun Lee ; Wonpil Im ; Hyun-Suk Lim
• 刊名：ACS Combinatorial Science
• 出版年：2016
• 出版时间：January 11, 2016
• 年：2016
• 卷：18
• 期：1
• 页码：36-42
• 全文大小：430K
• ISSN：2156-8944

文摘

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.