PMID- 16522339 OWN - NLM STAT- MEDLINE DCOM- 20060918 LR - 20061115 IS - 0168-1656 (Print) IS - 0168-1656 (Linking) VI - 125 IP - 1 DP - 2006 Aug 20 TI - De novo design TNF-alpha antagonistic peptide based on the complex structure of TNF-alpha with its neutralizing monoclonal antibody Z12. PG - 57-63 AB - 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. FAU - Qin, Weisong AU - Qin W AD - Institute of Basic Medical Sciences, P.O. Box 130 (3), Taiping Road, Beijing 100850, PR China. FAU - Feng, Jiannan AU - Feng J FAU - Li, Yan AU - Li Y FAU - Lin, Zhou AU - Lin Z FAU - Shen, Beifen AU - Shen B LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20060307 PL - Netherlands TA - J Biotechnol JT - Journal of biotechnology JID - 8411927 RN - 0 (Antibodies, Monoclonal) RN - 0 (Peptides) RN - 0 (Tumor Necrosis Factor-alpha) RN - EC 3.4.22.- (Caspases) SB - IM MH - Animals MH - Antibodies, Monoclonal/chemistry/immunology/*pharmacology MH - Caspases/metabolism MH - Cell Line, Tumor MH - Cell Survival/drug effects/immunology MH - Computer Simulation MH - Crystallography, X-Ray MH - *Drug Design MH - Enzyme Activation/drug effects MH - Enzyme-Linked Immunosorbent Assay MH - Humans MH - Models, Molecular MH - Peptides/chemical synthesis/chemistry/*pharmacology MH - Protein Structure, Tertiary MH - Tumor Necrosis Factor-alpha/*antagonists & inhibitors/chemistry/immunology EDAT- 2006/03/09 09:00 MHDA- 2006/09/19 09:00 CRDT- 2006/03/09 09:00 PHST- 2005/11/19 00:00 [received] PHST- 2005/12/30 00:00 [revised] PHST- 2006/01/20 00:00 [accepted] PHST- 2006/03/09 09:00 [pubmed] PHST- 2006/09/19 09:00 [medline] PHST- 2006/03/09 09:00 [entrez] AID - S0168-1656(06)00101-5 [pii] AID - 10.1016/j.jbiotec.2006.01.036 [doi] PST - ppublish SO - J Biotechnol. 2006 Aug 20;125(1):57-63. doi: 10.1016/j.jbiotec.2006.01.036. Epub 2006 Mar 7.