Peptide-Based Regulation of TNF-α-Mediated Cytotoxicity

Tumor necrosis factor alpha (TNF-α) is a pro-inflammatory cytokine associated with TNF receptor 1 (TNFR1) and TNF receptor 2 (TNFR2), which play important roles in several inflammatory diseases. There is a growing interest in developing alternative molecules that can be used as TNF blockers. In this...

Full description

Saved in:
Bibliographic Details
Main Authors: Betul Zehra Temur, Ahmet Can Timucin, Ahmet Emin Atik, Tanil Kocagoz, Ozge Can
Format: Article
Language:English
Published: MDPI AG 2025-04-01
Series:Biomolecules
Subjects:
Online Access:https://www.mdpi.com/2218-273X/15/4/559
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Tumor necrosis factor alpha (TNF-α) is a pro-inflammatory cytokine associated with TNF receptor 1 (TNFR1) and TNF receptor 2 (TNFR2), which play important roles in several inflammatory diseases. There is a growing interest in developing alternative molecules that can be used as TNF blockers. In this study, we focused on TNF-α-, TNFR1-, and TNFR2-mimicking peptides to inhibit TNF-α receptor binding in various ways. Six peptides (OB1, OB2, OB5, OB6, OB7, and OB8) were developed to bind TNFR1, TNFR2, and TNF-α. OB1 and OB2 bound to TNF-α with lower <i data-eusoft-scrollable-element="1">K</i><sub data-eusoft-scrollable-element="1">d</sub> values of 300 and 46.7 nM, respectively, compared to previously published sequences. These synthetic peptides directly and indirectly inhibited TNF-α in vitro without cytotoxicity to L929 cells, and OB1 significantly inhibited apoptosis in the presence of hTNF-α. Peptides developed in this study may prove to be useful for therapeutic inhibition of TNF-α.
ISSN:2218-273X