Current synthetic chemistry towards cyclic antimicrobial peptides

Area of Science:

• Biochemistry
• Medicinal Chemistry
• Pharmacology

Background:

• Antimicrobial peptides (AMPs) offer potential for novel antibiotics against multi-drug resistant (MDR) bacteria.
• Clinical use of AMPs is hindered by poor protease stability and high hemolytic toxicity.
• Strategies like amino acid replacement, backbone modification, cyclization, PEGylation, and lipidation are explored to enhance AMP properties.

Purpose of the Study:

• To review current strategies for synthesizing cyclic antimicrobial peptides (cAMPs).
• To analyze the impact of peptide cyclization on the biological activities of AMPs.
• To highlight cyclization as a promising approach for developing advanced antibiotic therapies.

Main Methods:

• Literature review of synthesis strategies for cyclic antimicrobial peptides.
• Analysis of published data on the influence of cyclization on AMP biostability and hemolytic toxicity.
• Evaluation of studies demonstrating enhanced target selectivity and antimicrobial activity of cyclic AMPs.

Main Results:

• Peptide cyclization significantly improves biostability and resistance to proteolytic degradation.
• Cyclization can modulate hemolytic toxicity and enhance target specificity of AMPs.
• Various cyclization strategies yield diverse cyclic AMPs with potent antimicrobial activities.

Conclusions:

• Peptide cyclization is a highly effective strategy to overcome AMP limitations like poor stability and toxicity.
• Cyclic antimicrobial peptides represent a promising class of therapeutics for combating multi-drug resistant bacterial infections.
• Further research into synthesis and biological evaluation of cyclic AMPs is warranted for clinical translation.