2. Academic Validation
  3. Novel peptide inhibitor of human tumor necrosis factor-α has antiarthritic activity

Novel peptide inhibitor of human tumor necrosis factor-α has antiarthritic activity

  • Sci Rep. 2024 Jun 5;14(1):12935. doi: 10.1038/s41598-024-63790-6.
Debasis Sahu # 1 2 3,  Charu Gupta # 4 5,  Ragothaman M Yennamalli 6,  Shikha Sharma 7 8,  Saugata Roy 5,  Sadaf Hasan 9,  Pawan Gupta 10,  Vishnu Kumar Sharma 11,  Sujit Kashyap 12 13,  Santosh Kumar 14,  Ved Prakash Dwivedi 14,  Xiangli Zhao 9 15,  Amulya Kumar Panda 16,  Hasi Rani Das 5,  Chuan-Ju Liu 9 15
Affiliations

Affiliations

  • 1 Product Development Cell, National Institute of Immunology, New Delhi, India. debasissahu.phd@gmail.com.
  • 2 Department of Orthopedics Surgery, New York University School of Medicine, New York, NY, USA. debasissahu.phd@gmail.com.
  • 3 Science Habitat, Ubioquitos Inc, London, ON, Canada. debasissahu.phd@gmail.com.
  • 4 School of Biomedical Sciences, Galgotias University, Greater Noida, UP, India.
  • 5 CSIR-Institute of Genomics and Integrative Biology, Delhi, India.
  • 6 Department of Bioinformatics, School of Chemical and Biotechnology, SASTRA Deemed to Be University, Thanjavur, Tamil Nadu, India.
  • 7 Amity Institute of Forensic Sciences, Amity University, Noida, Uttar Pradesh, India.
  • 8 Science Habitat, Ubioquitos Inc, London, ON, Canada.
  • 9 Department of Orthopedics Surgery, New York University School of Medicine, New York, NY, USA.
  • 10 Department of Pharmaceutical Chemistry, Shri Vile Parle Kelavani Mandal's Institute of Pharmacy, Dhule, Maharashtra, India.
  • 11 Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research (NIPER), Mohali, Punjab, India.
  • 12 Division of Pediatric Rheumatology, University of California San Francisco, San Francisco, CA, USA.
  • 13 Department of Genetics, University of Delhi, Delhi, India.
  • 14 Immunobiology Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India.
  • 15 Department of Orthopaedics and Rehabilitation, Yale University School of Medicine, New Haven, CT, USA.
  • 16 Product Development Cell, National Institute of Immunology, New Delhi, India.
  • # Contributed equally.
PMID: 38839973 DOI: 10.1038/s41598-024-63790-6
Abstract

The inhibition of tumor necrosis factor (TNF)-α 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 Flex-X) followed by molecular dynamics (MD) simulation studies. The MD studies confirmed the intermolecular interaction of the peptide with the TNFα. Fluorescence-activated cell sorting 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 gel mobility-shift assays. Furthermore, the peptide protected against joint damage in the collagen-induced arthritis (CIA) mouse model, as revealed in the micro focal-CT scans. In conclusion, this TNFα antagonist would be helpful for the prevention and repair of inflammatory 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 antiarthritic drug.

Keywords

Collagen-induced arthritis (CIA); Inflammation; Nuclear factor kappa B (NFκB); Peptide; Tumor necrosis factor (TNF)α.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z