Identification of novel peptides against TNF-α using phage display technique and in silico modeling of their modes of binding

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• 作者：Ali Akbar Alizadeh^a ; ^b ; Maryam Hamzeh-Mivehroud^a ; ^b ; ^{hamzehm@tbzmed.ac.ir} ; ^{maryam_h_7860@yahoo.com} ; Malak Farajzadeh^a ; Siavoush Dastmalchi^a ; ^b ; ^{dastmalchi.s@tbzmed.ac.ir} ; ^{siavoush11@yahoo.com}
• 关键词：ELISA ; enzyme-linked immunosorbent assay ; GST ; glutathione S-transferase ; IκB-α ; inhibitor of kappa B ; PLP ; piecewise linear potential
• 刊名：European Journal of Pharmaceutical Sciences
• 出版年：2017
• 出版时间：1 January 2017
• 年：2017
• 卷：96
• 期：Complete
• 页码：490-498
• 全文大小：867 K
• 卷排序：96

文摘

The aim of this study was to identify novel TNF-α blocking peptide(s) using phage display technology. Two novel 7-mer TNF-α binding peptides P51 and P52 with Kd values of 1.47 and 0.51 nM were identified. Phage particles displaying P51 and P52 peptides at 0.318 nM concentration prevent cytotoxic effect of TNF-α on L929 cells by 8.2% and 16.15%, respectively. Synthesized P51 and P52 peptides also inhibited TNF-α induced cytotoxicity with IC50 values of 25.15 ± 2.18 and 7.08 ± 2.24 μM, respectively. The result of RT-PCR also supports the inhibitory activity of the identified peptides, where P51 and P52 significantly inhibit the inductive effect of TNF-α on IκB-α mRNA levels. The inhibitory effects of the peptides were attributed to their abilities of binding at the inter-subunit interfaces leading to TNF-α dissociation. The results of molecular docking studies revealed that the peptides-TNF-α complexes are mostly stabilized by hydrophobic contacts.