Triazole-Bridged Peptides with Enhanced Antimicrobial Activity and Potency against Pathogenic Bacteria

Area of Science:

• Biochemistry
• Molecular Biology
• Medicinal Chemistry

Background:

• Linear antimicrobial peptides (AMPs) face challenges like poor proteolytic stability and low selectivity, hindering their clinical use.
• Existing AMPs often exhibit drawbacks that limit their efficacy as treatments for bacterial infections.

Purpose of the Study:

• To screen and develop novel antimicrobial peptides with improved stability and potency.
• To investigate the impact of introducing a triazole bridge on peptide structure, stability, and antimicrobial activity.

Main Methods:

• Screening a library of rationally designed peptides based on the cell-penetrating peptide sC18*.
• Introducing a triazole bridge into selected peptide structures to induce a preformed helical conformation.
• Evaluating antimicrobial activity against bacterial species and assessing tolerability against human cells.

Main Results:

• Identified novel effective antimicrobial peptides from the screened library.
• Peptides with a triazole bridge in the hydrophilic region demonstrated significantly increased membrane activity and proteolytic stability.
• The novel peptides 8A and 8B showed high activity against pathogenic *N. gonorrhoeae* and methicillin-resistant *S. aureus*.
• These peptides exhibited good tolerability against human fibroblast and blood cells.

Conclusions:

• The introduction of a triazole bridge is an effective strategy to enhance AMP stability and membrane activity.
• Novel peptides 8A and 8B represent promising candidates for future clinical applications in treating bacterial infections.
• Further studies are warranted to explore the full therapeutic potential of these modified AMPs.