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...
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MDPI AG
2025-04-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/15/4/559 |
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| author | Betul Zehra Temur Ahmet Can Timucin Ahmet Emin Atik Tanil Kocagoz Ozge Can |
| author_facet | Betul Zehra Temur Ahmet Can Timucin Ahmet Emin Atik Tanil Kocagoz Ozge Can |
| author_sort | Betul Zehra Temur |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-3bcce3b1baad4dcebfd00ee48787c434 |
| institution | OA Journals |
| issn | 2218-273X |
| language | English |
| publishDate | 2025-04-01 |
| publisher | MDPI AG |
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| series | Biomolecules |
| spelling | doaj-art-3bcce3b1baad4dcebfd00ee48787c4342025-08-20T02:17:20ZengMDPI AGBiomolecules2218-273X2025-04-0115455910.3390/biom15040559Peptide-Based Regulation of TNF-α-Mediated CytotoxicityBetul Zehra Temur0Ahmet Can Timucin1Ahmet Emin Atik2Tanil Kocagoz3Ozge Can4Department of Medical Biotechnology, Institute of Health Sciences, Acibadem Mehmet Ali Aydinlar University, Atasehir, 34752 Istanbul, TurkeyDepartment of Molecular Biology and Genetics, Faculty of Engineering and Natural Sciences, Acibadem Mehmet Ali Aydinlar University, Atasehir, 34752 İstanbul, TurkeyTurgut Ilaclari A.S., 41400 Kocaeli, TurkeyDepartment of Medical Biotechnology, Institute of Health Sciences, Acibadem Mehmet Ali Aydinlar University, Atasehir, 34752 Istanbul, TurkeyDepartment of Biomedical Engineering, Faculty of Engineering and Natural Sciences, Acibadem Mehmet Ali Aydinlar University, Atasehir, 34752 Istanbul, TurkeyTumor 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.https://www.mdpi.com/2218-273X/15/4/559TNF-αTNF-α receptorsTNF-α-binding peptideTNFR1-binding peptideTNFR2-binding peptideTNF-α inhibition |
| spellingShingle | Betul Zehra Temur Ahmet Can Timucin Ahmet Emin Atik Tanil Kocagoz Ozge Can Peptide-Based Regulation of TNF-α-Mediated Cytotoxicity Biomolecules TNF-α TNF-α receptors TNF-α-binding peptide TNFR1-binding peptide TNFR2-binding peptide TNF-α inhibition |
| title | Peptide-Based Regulation of TNF-α-Mediated Cytotoxicity |
| title_full | Peptide-Based Regulation of TNF-α-Mediated Cytotoxicity |
| title_fullStr | Peptide-Based Regulation of TNF-α-Mediated Cytotoxicity |
| title_full_unstemmed | Peptide-Based Regulation of TNF-α-Mediated Cytotoxicity |
| title_short | Peptide-Based Regulation of TNF-α-Mediated Cytotoxicity |
| title_sort | peptide based regulation of tnf α mediated cytotoxicity |
| topic | TNF-α TNF-α receptors TNF-α-binding peptide TNFR1-binding peptide TNFR2-binding peptide TNF-α inhibition |
| url | https://www.mdpi.com/2218-273X/15/4/559 |
| work_keys_str_mv | AT betulzehratemur peptidebasedregulationoftnfamediatedcytotoxicity AT ahmetcantimucin peptidebasedregulationoftnfamediatedcytotoxicity AT ahmeteminatik peptidebasedregulationoftnfamediatedcytotoxicity AT tanilkocagoz peptidebasedregulationoftnfamediatedcytotoxicity AT ozgecan peptidebasedregulationoftnfamediatedcytotoxicity |