Temur Betul Zehra, Timucin Ahmet Can, Atik Ahmet Emin, Kocagoz Tanil, Can Ozge
Department of Medical Biotechnology, Institute of Health Sciences, Acibadem Mehmet Ali Aydinlar University, Atasehir, 34752 Istanbul, Turkey.
Department of Molecular Biology and Genetics, Faculty of Engineering and Natural Sciences, Acibadem Mehmet Ali Aydinlar University, Atasehir, 34752 İstanbul, Turkey.
Biomolecules. 2025 Apr 10;15(4):559. doi: 10.3390/biom15040559.
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 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.
肿瘤坏死因子α（TNF-α）是一种促炎细胞因子，与TNF受体1（TNFR1）和TNF受体2（TNFR2）相关，它们在多种炎症性疾病中发挥重要作用。开发可作为TNF阻滞剂的替代分子的兴趣日益浓厚。在本研究中，我们专注于模拟TNF-α、TNFR1和TNFR2的肽，以多种方式抑制TNF-α受体结合。开发了六种肽（OB1、OB2、OB5、OB6、OB7和OB8）来结合TNFR1、TNFR2和TNF-α。与先前发表的序列相比，OB1和OB2分别以300 nM和46.7 nM的较低值结合TNF-α。这些合成肽在体外直接和间接抑制TNF-α，对L929细胞无细胞毒性，并且在存在hTNF-α的情况下，OB1显著抑制细胞凋亡。本研究中开发的肽可能被证明对TNF-α的治疗性抑制有用。
