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dc.contributor.authorGoodall, Cheri Peyton
dc.contributor.authorSchwartz, Benjamin
dc.contributor.authorSelivanovitch, Ekaterina
dc.contributor.authorAvera, John
dc.contributor.authorWang, Joseph
dc.contributor.authorMiettinen, Heini
dc.contributor.authorDouglas, Trevor
dc.date.accessioned2022-08-04T18:33:41Z
dc.date.available2022-08-04T18:33:41Z
dc.date.issued2021-11
dc.identifier.citationGoodall, C. P., Schwarz, B., Selivanovitch, E., Avera, J., Wang, J., Miettinen, H., & Douglas, T. (2021). Controlled modular multivalent presentation of the cd40 ligand on p22 virus-like particles leads to tunable amplification of cd40 signaling. ACS Applied Bio Materials, 4(12), 8205-8214.en_US
dc.identifier.issn2576-6422
dc.identifier.urihttps://scholarworks.montana.edu/xmlui/handle/1/16991
dc.description.abstractLigands of the tumor necrosis factor superfamily (TNFSF) are appealing targets for immunotherapy research due to their integral involvement in stimulation or restriction of immune responses. TNFSF-targeted therapies are currently being developed to combat immunologically based diseases and cancer. A crucial determinant of effective TNFSF receptor binding and signaling is the trimeric quaternary structure of the ligand. Additionally, ligand multivalency is essential to propagate strong signaling in effector cells. Thus, designing a synthetic platform to display trimeric TNFSF ligands in a multivalent manner is necessary to further the understanding of ligand–receptor interactions. Viral nanocages have architectures that are amenable to genetic and chemical modifications of both their interior and exterior surfaces. Notably, the exterior surface of virus-like particles can be utilized as a platform for the modular multivalent presentation of target proteins. In this study, we build on previous efforts exploring the bacteriophage P22 virus-like particle for the exterior multivalent modular display of a potent immune-stimulating TNFSF protein, CD40 ligand (CD40L). Using a cell-based reporter system, we quantify the effects of tunable avidity on CD40 signaling by CD40L displayed on the surface of P22 nanocages. Multivalent presentation of CD40L resulted in a 53.6-fold decrease of the half maximal effective concentration (EC50) compared to free CD40L, indicating higher potency. Our results emphasize the power of using P22-based biomimetics to study ligand−receptor interactions within their proper structural context, which may contribute to the development of effective immune modulators.en_US
dc.language.isoen_USen_US
dc.publisherAmerican Chemical Societyen_US
dc.rightscopyright © American Chemical Societyen_US
dc.titleControlled Modular Multivalent Presentation of the CD40 Ligand on P22 Virus-like Particles Leads to Tunable Amplification of CD40 Signalingen_US
dc.typeArticleen_US
mus.citation.extentfirstpage8205en_US
mus.citation.extentlastpage8214en_US
mus.citation.issue12en_US
mus.citation.journaltitleACS Applied Bio Materialsen_US
mus.citation.volume4en_US
mus.identifier.doi10.1021/acsabm.1c00718en_US
mus.relation.collegeCollege of Agricultureen_US
mus.relation.departmentMicrobiology & Cell Biology.en_US
mus.relation.universityMontana State University - Bozemanen_US
mus.data.thumbpage3en_US


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