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

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 K d 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 IC 50 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. [ABSTRACT FROM AUTHOR]