{"id":309,"date":"2020-01-02T19:28:17","date_gmt":"2020-01-02T19:28:17","guid":{"rendered":"https:\/\/wwwtest.pharmacy.wisc.edu\/faculty\/hong-research-group\/?p=309"},"modified":"2025-06-20T19:31:52","modified_gmt":"2025-06-20T19:31:52","slug":"nanoparticle-conjugation-stabilizes-and-multimerizes-%ce%b2-hairpin-peptides-to-effectively-target-pd-1-pd-l1-%ce%b2-sheet-rich-interfaces","status":"publish","type":"post","link":"https:\/\/pharmacy.wisc.edu\/faculty\/hong-research-group\/2020\/01\/02\/nanoparticle-conjugation-stabilizes-and-multimerizes-%ce%b2-hairpin-peptides-to-effectively-target-pd-1-pd-l1-%ce%b2-sheet-rich-interfaces\/","title":{"rendered":"Nanoparticle Conjugation Stabilizes and Multimerizes \u03b2-Hairpin Peptides To Effectively Target PD-1\/PD-L1 \u03b2-Sheet-Rich Interfaces"},"content":{"rendered":"

Abstract<\/h2>\r\n

\u03b2-Hairpin peptides present great potential as antagonists against \u03b2-sheet-rich protein surfaces, of which wide and flat geometries are typically \u201cundruggable\u201d with small molecules. Herein, we introduce a peptide\u2013dendrimer conjugate (PDC) approach that stabilizes the \u03b2-hairpin structure of the peptide via intermolecular forces and the excluded volume effect as well as exploits the multivalent binding effect. Because of the synergistic advantages, the PDCs based on a \u03b2-hairpin peptide isolated from an engineered programmed death-1 (PD-1) protein showed significantly higher affinity (avidity) to their binding counterpart, programmed death-ligand 1 (PD-L1), as compared to free peptides (by up to 5 orders of magnitude). The enhanced binding kinetics with high selectivity was translated into an improved immune checkpoint inhibitory effect in vitro, at a level comparable to (if not better than) that of a full-size monoclonal antibody. The results demonstrate the potential of the PDC system as a novel class of inhibitors targeting \u03b2-strand-rich protein surfaces, such as PD-1 and PD-L1, displaying its potential as a new cancer immunotherapy platform.<\/p>\r\n\"visualization\r\n\r\n

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Cited by<\/h2>\r\nThis article is cited by 11 publications\r\n
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    Gu, Z., Xu, S., Guo, Z., & Liu, Z. (2022). Rational development of molecularly imprinted nanoparticles for blocking PD-1\/PD-L1 axis.\u00a0Chemical science<\/i>,\u00a013<\/i>(36), 10897\u201310903.\u00a0https:\/\/doi.org\/10.1039\/d2sc03412c<\/a><\/div><\/li>\r\n \t
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    Poellmann, M. J., Rawding, P., Kim, D., Bu, J., Kim, Y., & Hong, S. (2022). Branched, dendritic, and hyperbranched polymers in liquid biopsy device design.\u00a0Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology<\/i>,\u00a014<\/i>(3), e1770.\u00a0https:\/\/doi.org\/10.1002\/wnan.1770<\/a><\/div><\/li>\r\n \t
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    Rawding, P. A., Bu, J., Wang, J., Kim, D. W., Drelich, A. J., Kim, Y., & Hong, S. (2022). Dendrimers for cancer immunotherapy: Avidity-based drug delivery vehicles for effective anti-tumor immune response.\u00a0Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology<\/i>,\u00a014<\/i>(2), e1752.\u00a0https:\/\/doi.org\/10.1002\/wnan.1752<\/a><\/div><\/li>\r\n \t
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    Jeong, W. J., Bu, J., Jafari, R., Rehak, P., Kubiatowicz, L. J., Drelich, A. J., Owen, R. H., Nair, A., Rawding, P. A., Poellmann, M. J., Hopkins, C. M., Kr\u00e1l, P., & Hong, S. (2022). Hierarchically Multivalent Peptide-Nanoparticle Architectures: A Systematic Approach to Engineer Surface Adhesion.\u00a0Advanced science (Weinheim, Baden-Wurttemberg, Germany)<\/i>,\u00a09<\/i>(4), e2103098.\u00a0https:\/\/doi.org\/10.1002\/advs.202103098<\/a><\/div><\/li>\r\n \t
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    Ershov, P. V., Mezentsev, Y. V., & Ivanov, A. S. (2022). Interfacial Peptides as Affinity Modulating Agents of Protein-Protein Interactions.\u00a0Biomolecules<\/i>,\u00a012<\/i>(1), 106.\u00a0https:\/\/doi.org\/10.3390\/biom12010106<\/a><\/div><\/li>\r\n \t
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    Nair, A., Bu, J., Bugno, J., Rawding, P. A., Kubiatowicz, L. J., Jeong, W. J., & Hong, S. (2021). Size-Dependent Drug Loading, Gene Complexation, Cell Uptake, and Transfection of a Novel Dendron-Lipid Nanoparticle for Drug\/Gene Co-delivery.\u00a0Biomacromolecules<\/i>,\u00a022<\/i>(9), 3746\u20133755.\u00a0https:\/\/doi.org\/10.1021\/acs.biomac.1c00541<\/a><\/div><\/li>\r\n \t
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    Liu, C., Seeram, N. P., & Ma, H. (2021). Small molecule inhibitors against PD-1\/PD-L1 immune checkpoints and current methodologies for their development: a review.\u00a0Cancer cell international<\/i>,\u00a021<\/i>(1), 239.\u00a0https:\/\/doi.org\/10.1186\/s12935-021-01946-4<\/a><\/div><\/li>\r\n \t
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    Li, L., Ma, B., & Wang, W. (2020). Peptide-Based Nanomaterials for Tumor Immunotherapy.\u00a0Molecules (Basel, Switzerland)<\/i>,\u00a026<\/i>(1), 132.\u00a0https:\/\/doi.org\/10.3390\/molecules26010132<\/a><\/div><\/li>\r\n \t
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    Skibba, M., Drelich, A., Poellmann, M., Hong, S., & Brasier, A. R. (2020). Nanoapproaches to Modifying Epigenetics of Epithelial Mesenchymal Transition for Treatment of Pulmonary Fibrosis.\u00a0Frontiers in pharmacology<\/i>,\u00a011<\/i>, 607689.\u00a0https:\/\/doi.org\/10.3389\/fphar.2020.607689<\/a><\/div><\/li>\r\n \t
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    Bu, J., Lee, T. H., Jeong, W. J., Poellmann, M. J., Mudd, K., Eun, H. S., Liu, E. W., Hong, S., & Hyun, S. H. (2020). Enhanced detection of cell-free DNA (cfDNA) enables its use as a reliable biomarker for diagnosis and prognosis of gastric cancer.\u00a0PloS one<\/i>,\u00a015<\/i>(12), e0242145.\u00a0https:\/\/doi.org\/10.1371\/journal.pone.0242145<\/a><\/div><\/li>\r\n \t
  11. \r\n
    Bu, J., Nair, A., Iida, M., Jeong, W. J., Poellmann, M. J., Mudd, K., Kubiatowicz, L. J., Liu, E. W., Wheeler, D. L., & Hong, S. (2020). An Avidity-Based PD-L1 Antagonist Using Nanoparticle-Antibody Conjugates for Enhanced Immunotherapy.\u00a0Nano letters<\/i>,\u00a020<\/i>(7), 4901\u20134909.\u00a0https:\/\/doi.org\/10.1021\/acs.nanolett.0c00953<\/a><\/div><\/li>\r\n<\/ol>","protected":false},"excerpt":{"rendered":"Abstract \u03b2-Hairpin peptides present great potential as antagonists against \u03b2-sheet-rich protein surfaces, of which wide and flat geometries are typically \u201cundruggable\u201d with small molecules. Herein, we introduce a peptide\u2013dendrimer conjugate (PDC) approach that stabilizes the …","protected":false},"author":7,"featured_media":311,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[4],"tags":[],"class_list":["post-309","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-publications"],"acf":[],"_links":{"self":[{"href":"https:\/\/pharmacy.wisc.edu\/faculty\/hong-research-group\/wp-json\/wp\/v2\/posts\/309","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/pharmacy.wisc.edu\/faculty\/hong-research-group\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/pharmacy.wisc.edu\/faculty\/hong-research-group\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/pharmacy.wisc.edu\/faculty\/hong-research-group\/wp-json\/wp\/v2\/users\/7"}],"replies":[{"embeddable":true,"href":"https:\/\/pharmacy.wisc.edu\/faculty\/hong-research-group\/wp-json\/wp\/v2\/comments?post=309"}],"version-history":[{"count":1,"href":"https:\/\/pharmacy.wisc.edu\/faculty\/hong-research-group\/wp-json\/wp\/v2\/posts\/309\/revisions"}],"predecessor-version":[{"id":312,"href":"https:\/\/pharmacy.wisc.edu\/faculty\/hong-research-group\/wp-json\/wp\/v2\/posts\/309\/revisions\/312"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/pharmacy.wisc.edu\/faculty\/hong-research-group\/wp-json\/wp\/v2\/media\/311"}],"wp:attachment":[{"href":"https:\/\/pharmacy.wisc.edu\/faculty\/hong-research-group\/wp-json\/wp\/v2\/media?parent=309"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/pharmacy.wisc.edu\/faculty\/hong-research-group\/wp-json\/wp\/v2\/categories?post=309"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/pharmacy.wisc.edu\/faculty\/hong-research-group\/wp-json\/wp\/v2\/tags?post=309"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}