De novo design TNF-α antagonistic peptide based on the complex structure of TNF-α with its neutralizing monoclonal antibody Z12
Tumor necrosis factor-α(TNF-α) antagonists have become therapeutic drugs for immunological diseases including rheumatoid arthritis, inflammatory bowel disease. Crohns disease, etc. Low molecular weight synthetic peptides can mimic (he binding sites of TNF-α receptors and block the activity of TNF-α. Based on the 3-D complex structure of TNF-α 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-α, TNF-α-meditated caspase activation and TNF-α-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-α.
TNF-α Antagonistic peptide De novo design Molecular modeling
Wei song Qin Jiannan Feng Yan Li Zhou Lin Beifen Shen
Institute of Basic Medical Sciences, P.O. Box 130 (3), Taiping Road, Beijing 100850, PR China
国际会议
杭州
英文
960-966
2007-04-01（万方平台首次上网日期，不代表论文的发表时间）