Discovery of peptidic miR-21 processing inhibitor by mirror image phage display: A novel method to generate RNA binding D-peptides

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• 作者：Kotaro Sakamoto ; Kentaro Otake ; Tadashi Umemoto ; ^{tadashi.umemoto@takeda.com}
• 关键词：Peptide ; miRNA ; Phage display ; Mirror image ; D-amino acid
• 刊名：Bioorganic & Medicinal Chemistry Letters
• 出版年：2017
• 出版时间：15 February 2017
• 年：2017
• 卷：27
• 期：4
• 页码：826-828
• 全文大小：825 K
• 卷排序：27

文摘

A novel method to generate RNA binding D-peptide has been developed. To achieve the screening method, phage display was applied to “Mirrored” RNA (L-enantiomer of RNA). We have selected pre-miR21 as an initial screening target to demonstrate the method. The mirrored pre-miR-21 binding peptide sequences were successfully obtained, and were chemically synthesized using D-amino acids. D-peptide is expected to have favorable properties as a drug candidate such as protease resistance and low immunogenicity. As a result of binding evaluation of the D-peptide to pre-miR-21, the EC50 value was 440 nM. In addition, the D-peptide possessed inhibition activity to miR-21 processing.