Peptide-Based Regulation of TNF-α-Mediated Cytotoxicity

TEMUR B. Z., TİMUÇİN V. C., ATİK A. E., KOCAGÖZ Z. T., CAN Ö.

Biomolecules, cilt.15, sa.4, 2025 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 15 Sayı: 4
  • Basım Tarihi: 2025
  • Doi Numarası: 10.3390/biom15040559
  • Dergi Adı: Biomolecules
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, Food Science & Technology Abstracts, MEDLINE, Veterinary Science Database, Directory of Open Access Journals
  • Anahtar Kelimeler: TNF-α, TNF-α blocker, TNF-α inhibition, TNF-α receptors, TNF-α-binding peptide, TNFR1-binding peptide, TNFR2-binding peptide
  • Acıbadem Mehmet Ali Aydınlar Üniversitesi Adresli: Evet

Özet

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 Kd 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.