De novo design TNF-α antagonistic peptide based on the complex structure of TNF-α with its neutralizing monoclonal antibody Z12
Copyright policy )De novo design TNF-α antagonistic peptide based on the complex structure of TNF-α with its neutralizing monoclonal antibody Z12
Tumor necrosis factor-alpha (TNF-alpha) antagonists have become therapeutic drugs for immunological diseases including rheumatoid arthritis, inflammatory bowel disease, Crohn's disease, etc. Low molecular weight synthetic peptides can mimic the binding sites of TNF-alpha receptors and block the activity of TNF-alpha. Based on the 3-D complex structure of TNF-alpha with its neutralizing monoclonal antibody (Mab) Z12, an antagonistic peptide (AP) was rationally de novo designed. The designed AP possessed similar structural character and potential bioactivity with Mab Z12. AP could competitively inhibit the binding of Mab Z12 to TNF-alpha, TNF-alpha-meditated caspase activation and TNF-alpha-induced cytotoxicity on murine L929 cells with a dose-dependent fashion. This study highlights the potential of computation-aided method for the design of novel peptides with the ability to block the deleterious biological effects of TNF-alpha.
Models, Molecular, Cell Survival, Tumor Necrosis Factor-alpha, Antibodies, Monoclonal, Enzyme-Linked Immunosorbent Assay, Crystallography, X-Ray, Protein Structure, Tertiary, Enzyme Activation, Caspases, Cell Line, Tumor, Drug Design, Animals, Humans, Computer Simulation, Peptides
Models, Molecular, Cell Survival, Tumor Necrosis Factor-alpha, Antibodies, Monoclonal, Enzyme-Linked Immunosorbent Assay, Crystallography, X-Ray, Protein Structure, Tertiary, Enzyme Activation, Caspases, Cell Line, Tumor, Drug Design, Animals, Humans, Computer Simulation, Peptides
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