IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-54902-x.html
   My bibliography  Save this article

Generating a mirror-image monobody targeting MCP-1 via TRAP display and chemical protein synthesis

Author

Listed:
  • Gosuke Hayashi

    (Nagoya University)

  • Toshinori Naito

    (Nagoya University)

  • Sayaka Miura

    (Nagoya University)

  • Naoya Iwamoto

    (Kyoto University)

  • Yusuke Usui

    (Kyoto University)

  • Mika Bando-Shimizu

    (Kyoto University)

  • Sae Suzuki

    (Nagoya University)

  • Katsuaki Higashi

    (Kyoto University)

  • Motohiro Nonaka

    (Kyoto University)

  • Shinya Oishi

    (Kyoto University
    Kyoto Pharmaceutical University)

  • Hiroshi Murakami

    (Nagoya University
    Nagoya University
    Nagoya University)

Abstract

Biologically produced protein drugs are generally susceptible to degradation by proteases and often exhibit immunogenicity. To address this issue, mirror-image peptide/protein binders consisting of D-amino acids have been developed so far through the mirror-image phage display technique. Here, we develop a mirror-image protein binder derived from a monobody, one of the promising protein scaffolds, utilizing two notable technologies: chemical protein synthesis and TRAP display, an improved version of mRNA display. A sequential workflow of initial screening followed by affinity maturation, facilitated by TRAP display, generates an L-monobody with high affinity (KD = 1.3 nM) against monocyte chemoattractant protein-1 (MCP-1) D-enantiomer. The chemically synthesized D-monobody demonstrates strong and specific binding to L-MCP-1 and exhibits pharmaceutically favorable properties such as proteolytic resistance, minimal immune response, and a potent inhibitory effect on MCP-1-induced cell migration. This study elevates the value of mirror-image peptide/protein binders as an alternative modality in drug discovery.

Suggested Citation

  • Gosuke Hayashi & Toshinori Naito & Sayaka Miura & Naoya Iwamoto & Yusuke Usui & Mika Bando-Shimizu & Sae Suzuki & Katsuaki Higashi & Motohiro Nonaka & Shinya Oishi & Hiroshi Murakami, 2024. "Generating a mirror-image monobody targeting MCP-1 via TRAP display and chemical protein synthesis," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-54902-x
    DOI: 10.1038/s41467-024-54902-x
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-54902-x
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-54902-x?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-54902-x. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.