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De novo design TNF-α antagonistic peptide based on the complex structure of TNF-α with its neutralizing monoclonal antibody Z12

Paper ID Volume ID Publish Year Pages File Format Full-Text
25236 43562 2006 7 PDF Available
Title
De novo design TNF-α antagonistic peptide based on the complex structure of TNF-α with its neutralizing monoclonal antibody Z12
Abstract

Tumor necrosis factor-α (TNF-α) 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-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.

Keywords
TNF-α; Antagonistic peptide; De novo design; Molecular modeling
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De novo design TNF-α antagonistic peptide based on the complex structure of TNF-α with its neutralizing monoclonal antibody Z12
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Publisher
Database: Elsevier - ScienceDirect
Journal: Journal of Biotechnology - Volume 125, Issue 1, 20 August 2006, Pages 57–63
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us