2. Academic Validation
  3. Antibacterial, Antibiofilm, and Anti-inflammatory Effects of a Novel Thrombin-Derived Peptide in Sepsis Models: Insights into Underlying Mechanisms

Antibacterial, Antibiofilm, and Anti-inflammatory Effects of a Novel Thrombin-Derived Peptide in Sepsis Models: Insights into Underlying Mechanisms

  • J Med Chem. 2024 Nov 14;67(21):19791-19812. doi: 10.1021/acs.jmedchem.4c02157.
S Dinesh Kumar 1,  Jin Kyeong Lee 2,  Naveen Kumar Radhakrishnan 3,  Jeong Kyu Bang 4 5,  Byeongkwon Kim 2,  Shubhash Chandra Chaudhary 2,  Ajish Chelladurai 1,  Byambasuren Ganbaatar 6,  Eun Young Kim 1,  Chul Won Lee 6,  Sungtae Yang 7 8,  Yangmee Kim 2,  Song Yub Shin 1
Affiliations

Affiliations

  • 1 Department of Cellular & Molecular Medicine, School of Medicine, Chosun University, Gwangju 61452, Republic of Korea.
  • 2 Department of Bioscience and Biotechnology, Konkuk University, 120 Neungdong-ro, Seoul 05029, Republic of Korea.
  • 3 Graduate School of Biomedical Science, Chosun University, Gwangju 61452, Republic of Korea.
  • 4 Division of Magnetic Resonance, Korea Basic Science Institute (KBSI), Ochang, Chung Buk 28119, Republic of Korea.
  • 5 Dandicure Inc, Ochang, Chung Buk 28119, Republic of Korea.
  • 6 Department of Chemistry, Chonnam National University, Gwangju 61186, Republic of Korea.
  • 7 Department of Microbiology, School of Medicine, Chosun University, Gwangju 61452, Republic of Korea.
  • 8 Institute of Well-Aging Medicare & CSU G-LAMP Project Group, Chosun University, Gwangju 61452, Republic of Korea.
PMID: 39475485 DOI: 10.1021/acs.jmedchem.4c02157
Abstract

We developed two short helical antimicrobial peptides, HVF18-a3 and its d-enantiomer, HVF18-a3-d, derived from the Thrombin C-terminal peptide HVF18. These peptides exhibit potent antimicrobial activity against various bacteria by compromising both the outer and inner membranes, with low hemolytic activity. They are stable in the presence of physiological salts and human serum, exhibiting a low potential for developing drug resistance and excellent antibiofilm activity against Gram-negative bacteria. HVF18-a3-d also neutralized lipopolysaccharide (LPS) through direct binding interactions and suppressed the production of inflammatory cytokines through the inflammatory signaling pathway mediated by Toll-like Receptor 4 in RAW264.7 cells stimulated with LPS. Both pre- and post-treatment with HVF18-a3-d significantly protected mice against fatal septic shock induced by carbapenem resistant Acinetobacter baumannii. These findings suggest HVF18-a3 and HVF18-a3-d are promising candidates for developing Antibiotics against Gram-negative sepsis.

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