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Computer-Aided Design of Short Peptide Ligands Targeting Tumor Necrosis Factor-Alpha for Adsorbents Applications

Abstract

Tumor necrosis factor alpha (TNF-α) is a pro-inflammatory cytokine in the bodily immune response and serious inflammatory diseases. Traditional ligands targeting TNF-α focus on antibodies and receptors, which always associate with low efficacy and specificity. In the present study, two peptide ligands (T1: Ac-RKEM-NH2 and T2: Ac-RHCLS-NH2) were designed by computer simulation technology considering the weak interactions between TNF-α and its receptor TNFR-1. Calculations of binding free energy (BFE) were made by the Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) method between T1 and T2, and TNF-α (-22.68 and -14.23 kcal mol-1, respectively). To assess the affinity levels, the short peptide ligands were fixed on polyvinyl alcohol (PVA) microspheres; adsorption tests showed a stronger affinity of both PVA-T1 and PVA-T2 to TNF-α in PBS buffer compared to PVA microspheres (79.20 ± 1.32 and 74.27 ± 1.10 vs. 39.03 ± 1.25 pg mg-1, respectively). Moreover, PVA-T1 (74.8 %, 17.60 ± 2.98 pg mg-1) and PVA-T2 (63.2 %, 15.30 ± 4.81 pg mg-1) exhibit significantly enhanced TNF-α adsorption from sepsis rat plasma to blank PVA and commercial XAD-7 resin. In conclusion, our results show that T1 designed by computer-aided molecular design (CAMD) exhibit a stronger affinity to TNF- α and it can significantly enhance PVA microspheres adsorption efficiency of TNF-α in plasma.

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Publication details

The article was received on 01 Mar 2018, accepted on 07 Jun 2018 and first published on 07 Jun 2018


Article type: Paper
DOI: 10.1039/C8TB00563J
Citation: J. Mater. Chem. B, 2018, Accepted Manuscript
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    Computer-Aided Design of Short Peptide Ligands Targeting Tumor Necrosis Factor-Alpha for Adsorbents Applications

    J. Chen, J. Sun, W. Han, J. Chen, W. Wang, G. Cheng, J. Lin, L. Ou, W. Li and N. Ma, J. Mater. Chem. B, 2018, Accepted Manuscript , DOI: 10.1039/C8TB00563J

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