Novel Peptide Inhibitor of Human Tumor Necrosis Factor-α has Antiarthritic Activity-Reference-Cited by-同舟云学术

Novel Peptide Inhibitor of Human Tumor Necrosis Factor-α has Antiarthritic Activity

Published:2023-01-06 Issue: Volume: Page:
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Author:

Sahu Debasis¹,Gupta Charu²,Yennamalli Ragothaman M.³,Sharma Shikha⁴,Roy Saugata⁵,Hasan Sadaf⁶,Gupta Pawan⁷,Sharma Vishnu Kumar⁸,Kashyap Sujit⁹,Kumar Santosh¹⁰,Dwivedi Ved Prakash¹⁰,Panda Amulya Kumar¹,Das Hasi Rani⁵,Liu Chuan-Ju⁶

Affiliation:

1. National Institute of Immunology

2. Galgotias University

3. SASTRA deemed to be University

4. Amity University

5. CSIR-Institute of Genomics and Integrative Biology

6. New York University School of Medicine

7. Shri Vile Parle Kelavani Mandal’s Institute of Pharmacy

8. National Institute of Pharmaceutical Education and Research (NIPER)

9. University of California San Francisco

10. International Centre for Genetic Engineering and Biotechnology

Abstract

Abstract The inhibition of tumor necrosis factor-α (TNFα) trimer formation renders it inactive for binding to its receptors thus mitigating the vicious cycle of inflammation. We designed a peptide (PIYLGGVFQ) that simulates a sequence strand of human TNFα monomer using a series of in silico methods, such as active site finding (Acsite), protein-protein interaction (PPI), docking studies (GOLD and Modeller) followed by molecular dynamics (MD) simulation studies. The MD studies confirmed the intermolecular interaction of the peptide with the TNFα. Fluorescence-activated cell sorting (FACS) and fluorescence microscopy revealed that the peptide effectively inhibited the binding of TNF to the cell surface receptors. The cell culture assays showed that the peptide significantly inhibited the TNFα-mediated cell death. In addition, the nuclear translocation of the nuclear factor kappa B (NFκB) was significantly suppressed in the peptide-treated A549 cells as observed in immunofluorescence and gelmobility-shift assays. Furthermore, peptide protected against joint damage in collagen-induced arthritis (CIA)mouse model as revealed in the microfocal-CT scans. In conclusion, this TNFα antagonist would be useful for the prevention and repair ofinflammatory bone destruction and subsequent loss in the mouse model of CIA as well as human rheumatoid arthritis (RA) patients. This calls upon further clinical investigation to utilize its potential effect as an anti-arthritic drug.

Publisher

Research Square Platform LLC

Reference48 articles.

1. F. Mackay and S. L. Kalled, “TNF ligands and receptors in autoimmunity: an update,” Curr. Opin. Immunol., vol. 14, no. 6, pp. 783–790, Dec. 2002.

2. E. Abraham, “Cytokine modifiers: pipe dream or reality?,” Chest, vol. 113, no. 3 Suppl, pp. 224S-227S, Mar. 1998.

3. A. D’Souza, B. L. Meissner, B. Tang, R. S. McKenzie, and C. T. Piech, “Effectiveness of Anti-Tumor Necrosis Factor Agents in the Treatment of Rheumatoid Arthritis: Observational Study,” Am. Heal. Drug Benefits, vol. 3, no. 4, p. 266, Jul. 2010.

4. N. Trier, P. Hansen, and G. Houen, “Peptides, Antibodies, Peptide Antibodies and More,” Int. J. Mol. Sci., vol. 20, no. 24, Dec. 2019.

5. M. Rarey, B. Kramer, T. Lengauer, and G. Klebe, “A Fast Flexible Docking Method using an Incremental Construction Algorithm,” J. Mol. Biol., vol. 261, no. 3, pp. 470–489, Aug. 1996.