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Discovery of Tumor Necrosis Factor Receptor Binders using Yeast Surface Display
Author(s) -
Vunnam Nagamani,
Szymonski Sophia,
Sachs Jonathan N.,
Hackel Benjamin
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.798.18
Subject(s) - receptor , tumor necrosis factor alpha , tumor necrosis factor receptor , phage display , ligand (biochemistry) , microbiology and biotechnology , biology , cancer research , computational biology , immunology , biochemistry , antibody
Tumor Necrosis Factor Receptors (TNFRs) are essential regulators of the immune system. Dysregulation of TNF receptors play a role in the pathology of many autoimmune diseases. Available treatments for TNF‐related diseases cause adverse side effects by unintentionally inhibiting ligand binding to off‐target receptors. In our previous work we showed an alternative therapeutic strategy for inhibition of the pro‐apoptotic activities of TNF receptors by specifically targeting receptor‐receptor interactions, without interrupting ligand binding. In the current study, we employed two small protein scaffold libraries, T7 phage gene 2 protein (Gp2) and affibody, to discover binders that specifically modulate the signaling activities of death receptor 5 (DR5) and TNFR1. Using yeast display and directed evolution, we will identify Gp2 and affibody variants with high binding affinity, stability and specificity to DR5 and TNFR1. These small protein scaffolds can be used as therapeutic agents in TNFR related diseases. Support or Funding Information NIH 1R01 EB023339‐01 This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .