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Bifunctional Peptide that Anneals to Damaged Collagen and Clusters TGF-β Receptors Enhances Wound Healing
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    Bifunctional Peptide that Anneals to Damaged Collagen and Clusters TGF-β Receptors Enhances Wound Healing
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    • Sayani Chattopadhyay
      Sayani Chattopadhyay
      Department of Chemistry, University of Wisconsin−Madison, Madison, Wisconsin 53706, United States
    • Leandro B. C. Teixeira
      Leandro B. C. Teixeira
      Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin−Madison, Madison, Wisconsin 53706, United States
    • Laura L. Kiessling
      Laura L. Kiessling
      Department of Chemistry, University of Wisconsin−Madison, Madison, Wisconsin 53706, United States
      Department of Biochemistry, University of Wisconsin−Madison, Madison, Wisconsin 53706, United States
      Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States
    • Jonathan F. McAnulty
      Jonathan F. McAnulty
      Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin−Madison, Madison, Wisconsin 53706, United States
    • Ronald T. Raines*
      Ronald T. Raines
      Department of Chemistry, University of Wisconsin−Madison, Madison, Wisconsin 53706, United States
      Department of Biochemistry, University of Wisconsin−Madison, Madison, Wisconsin 53706, United States
      Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States
      *Email: [email protected]
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    ACS Chemical Biology

    Cite this: ACS Chem. Biol. 2022, 17, 2, 314–321
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    https://doi.org/10.1021/acschembio.1c00745
    Published January 27, 2022
    Copyright © 2022 American Chemical Society

    Abstract

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    Transforming growth factor-β (TGF-β) plays important roles in wound healing. The activity of TGF-β is initiated upon the binding of the growth factor to the extracellular domains of its receptors. We sought to facilitate the activation by clustering these extracellular domains. To do so, we used a known peptide that binds to TGF-β receptors without diminishing their affinity for TGF-β. We conjugated this peptide to a collagen-mimetic peptide that can anneal to the damaged collagen in a wound bed. We find that the conjugate enhances collagen deposition and wound closure in mice in a manner consistent with the clustering of TGF-β receptors. This strategy provides a means to upregulate the TGF-β signaling pathway without adding exogenous TGF-β and could inspire means to treat severe wounds.

    Copyright © 2022 American Chemical Society

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    This article is cited by 10 publications.

    1. Jinyi Yang, Yifan Quan, Yifu Ouyang, Kong Ooi Tan, Ralph T. Weber, Robert G. Griffin, Ronald T. Raines. Peptidic “Molecular Beacon” for Collagen. Biomacromolecules 2024, 25 (10) , 6773-6779. https://doi.org/10.1021/acs.biomac.4c01000
    2. Xiaojing Li, Qi Zhang, S. Michael Yu, Yang Li. The Chemistry and Biology of Collagen Hybridization. Journal of the American Chemical Society 2023, 145 (20) , 10901-10916. https://doi.org/10.1021/jacs.3c00713
    3. Anaïs Terrien, Keyvan Rahgoshay, Emelyne Renaglia, Nathalie Lensen, Yves Jacquot, Rodrigue Marquant, Thierry Brigaud, Claire Loison, Grégory Chaume, Emeric Miclet. Inviting C5-Trifluoromethylated Pseudoprolines into Collagen Mimetic Peptides. Biomacromolecules 2023, 24 (4) , 1555-1562. https://doi.org/10.1021/acs.biomac.2c01242
    4. Juthatip Manissorn, Jaturong Promsuk, Kittikhun Wangkanont, Peerapat Thongnuek. Biomimetic peptide conjugates as emerging strategies for controlled release from protein-based materials. Drug Delivery 2025, 32 (1) https://doi.org/10.1080/10717544.2025.2449703
    5. Jeremy C. Tran, Christopher J. Kuffner, Alexander M. Marzilli, Ryan Emily Miller, Zachary E. Silfen, Jeffrey B. McMahan, D. Christopher Sloas, Christopher S. Chen, John T. Ngo. Fluorescein-based SynNotch adaptors for regulating gene expression responses to diverse extracellular and matrix-based cues. Nature Communications 2025, 16 (1) https://doi.org/10.1038/s41467-025-56148-7
    6. Alireza Ghofrani, Zahra Hassannejad. Collagen-Based Therapies for Accelerated Wound Healing. 2024https://doi.org/10.5772/intechopen.1004079
    7. Menglong Liu, Rui Ding, Zheng Li, Na Xu, Yali Gong, Yong Huang, Jiezhi Jia, Haiyan Du, Yunlong Yu, Gaoxing Luo. Hyaluronidase‐Responsive Bactericidal Cryogel for Promoting Healing of Infected Wounds: Inflammatory Attenuation, ROS Scavenging, and Immune Regulation. Advanced Science 2024, 11 (17) https://doi.org/10.1002/advs.202306602
    8. Houpu Li, Hsin‐ya Yang, Narges Asefifeyzabadi, Prabhat Baniya, Andrea Medina Lopez, Anthony Gallegos, Kan Zhu, Tiffany Nguyen, Cristian Hernandez, Ksenia Zlobina, Cynthia Recendez, Hao‐Chieh Hsieh, Maryam Tebyani, Héctor Carrión, John Selberg, Le Luo, Moyasar A. Alhamo, Alexie Barbee, Jonathan Orozco, Cathleen Hsieh, Athena M. Soulika, Michael Levin, Narges Norouzi, Marcella Gomez, Min Zhao, Mircea Teodorescu, Roslyn Rivkah Isseroff, Marco Rolandi. Programmable Delivery of Fluoxetine via Wearable Bioelectronics for Wound Healing In Vivo. Advanced Materials Technologies 2024, 9 (7) https://doi.org/10.1002/admt.202301115
    9. Barani Karikalan, Srikumar Chakravarthi. Genes involved in chronic wound healing and their therapeutic potential. IP Archives of Cytology and Histopathology Research 2023, 8 (2) , 83-89. https://doi.org/10.18231/j.achr.2023.020
    10. Variksha Singh, Thashree Marimuthu, Maya M. Makatini, Yahya E. Choonara. Biopolymer-Based Wound Dressings with Biochemical Cues for Cell-Instructive Wound Repair. Polymers 2022, 14 (24) , 5371. https://doi.org/10.3390/polym14245371

    ACS Chemical Biology

    Cite this: ACS Chem. Biol. 2022, 17, 2, 314–321
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acschembio.1c00745
    Published January 27, 2022
    Copyright © 2022 American Chemical Society

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