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Fine tuning of receptor-selectivity for tumor necrosis factor-α using a phage display system with one-step competitive panning

Paper ID Volume ID Publish Year Pages File Format Full-Text
8218 581 2011 7 PDF Available
Title
Fine tuning of receptor-selectivity for tumor necrosis factor-α using a phage display system with one-step competitive panning
Abstract

Tumor necrosis factor-α (TNF) is one of the attractive targets for the development of anti-inflammatory and anti-tumor drugs, because it is an important mediator in the pathogenesis of several inflammatory diseases and tumor progression. Thus, there is an increasing need to understand the TNF receptor (TNFR1 and TNFR2) biology for the development of TNFR-selective drugs. Nonetheless, the role of TNFRs, especially that of TNFR2, remains poorly understood. Here, using a unique competitive panning, we optimized our phage display-based screening technique for isolating receptor-selective TNF mutants, and identified several TNFR2-specific TNF mutants with high TNFR2 affinity and full bioactivity via TNFR2. Among these mutants, the R2-7 clone revealed very high TNFR2-selectivity (1.8 × 105 fold higher than that for the wild-type TNF), which is so far highest among the reported TNFR2-selective TNF mutants. Because of its high TNFR2-selectivity and full bioactivity, the TNF mutant R2-7 would not only help in elucidating the functional role of TNFR2 but would also help in understanding the structure-function relationship of TNF/TNFR2. In summary, our one-step competitive panning system is a simple, useful and effective technology for isolating receptor-selective mutant proteins.

Keywords
Cytokine; Molecular biology; Protein; Affinity; Bioactivity
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Fine tuning of receptor-selectivity for tumor necrosis factor-α using a phage display system with one-step competitive panning
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 32, Issue 23, August 2011, Pages 5498–5504
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