Multifunctional cyclic biomimetic peptides: Self-assembling nanotubes for effective treatment of sepsis
International Journal of Biological Macromolecules, ISSN: 0141-8130, Vol: 288, Page: 138522
2025
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Article Description
Antibiotic abuse has led to an increasingly serious risk of antimicrobial resistance, developing alternative antimicrobials to combat this alarming issue is urgently needed. Rhesus theta defensin-1 (RTD-1) is a theta-defensin contributing to broad-spectrum bactericidal activity via the mechanisms of membrane perturbation. Intriguingly, human defensin-6 (HD6), an enteric defensin secreted by Paneth cells without direct bactericidal effect, could self-assembled into fibrous networks to trap enteric pathogens for assistance of innate immunity. The direct bactericidal action of RTD-1 and the bacterial trapping of HD6 inspire a promising antimicrobial paradigm for unique antibacterial strategies. In this study, we utilized the principle of alternating arrangement of D- and L-amino acids in cyclic peptides, which endows them with the potential to self-assemble into nanotubes, mimic the antimicrobial processes of RTD-1 and HD6. We designed and synthesized five cyclic biomimetic peptides (CBPs), among these biomimetics, CBP-4, which possessed a nanotube-like structure, demonstrated the ability to directly and rapidly disrupt the cell membranes of Gram-positive S. aureus and MRSA, while also targeting the surfaces of Gram-negative E. coil using its nanofibrous network to capture bacteria, preventing invasion and migration, and indirectly killing the bacteria. Moreover, CBP-4 eliminated pathogens, inhibited excessive inflammatory responses caused by infections, and maintained immune system homeostasis in septic mice. By fully emulating the antimicrobial mechanisms of both RTD-1 and HD6, CBP-4 showed promising potential for anti-infectious therapies.
Bibliographic Details
http://www.sciencedirect.com/science/article/pii/S0141813024093334; http://dx.doi.org/10.1016/j.ijbiomac.2024.138522; http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85212091331&origin=inward; http://www.ncbi.nlm.nih.gov/pubmed/39672431; https://linkinghub.elsevier.com/retrieve/pii/S0141813024093334; https://dx.doi.org/10.1016/j.ijbiomac.2024.138522
Elsevier BV
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