Utilizing Proteolytic-Resistant Nano-Short Peptide Based on Naphthyl Tail-Anchored to Combat Bacterial Infections

Area of Science:

• Biomaterials Science
• Medicinal Chemistry
• Nanotechnology

Background:

• Antimicrobial peptides (AMPs) show promise as antibiotic alternatives but are degraded by proteases.
• Developing protease-resistant AMPs is crucial for effective therapeutic applications.

Purpose of the Study:

• To engineer potent, protease-resistant nano-short peptides based on the "RDRRP" motif.
• To investigate the self-assembly properties and antimicrobial efficacy of naphthyl tail-anchored peptides.

Main Methods:

• Design and synthesis of nano-short peptides with hydrophobic groups and naphthyl tails.
• Analysis of bioactivity, nanoproperties, and biostability against proteases and physiological conditions.
• Evaluation of antimicrobial mechanisms, including membrane disruption and energy metabolism interference.
• In vivo efficacy testing in mouse models of sepsis (E. coli) and skin infection (MRSA).

Main Results:

• Naphthyl tail-anchored N4 peptide self-assembles into nanofibers in aqueous solutions.
• Demonstrated potent, broad-spectrum antimicrobial activity (GM_MIC = 5.04) with excellent biocompatibility (GM_SI = 50.8).
• Exhibited remarkable biostability against salt, serum, and proteases.
• Showed low resistance propensity due to multiple antimicrobial mechanisms.
• Successfully treated E. coli-induced sepsis and MRSA skin infections in mice.

Conclusions:

• Naphthyl tail anchoring is a valid strategy for creating self-assembling, protease-resistant AMPs.
• The engineered N4 peptide offers a promising candidate for developing novel peptide-based nanomaterials.
• Findings advance AMP design for enhanced stability and potential biomedical applications.