Given the low bioavailability of relevant AMPs in nature, biotechnological interventions with genetic engineering and synthetic biology strategies for enhanced AMP synthesis have been a key focus in industry . With this, as synthetic peptide development approaches have improved, the potential of synthetic AMPs to counteract pathogens and emerging infections has grown – they can now be designed with multifaceted mechanisms of action and act as antiviral, antibacterial and antifungal agents.
Key categories of AMPs currently in development include receptor-binding peptides, membrane-active peptides, membrane-lytic peptides and inhibitory peptides (such as cell wall-inhibiting peptides) . AMPs generally affect highly preserved structures and can be used against specific targets such as peptidoglycans in Gram-negative and Gram-positive bacteria, and glucan in the fungal cell wall. Other peptides are particularly active on biofilm destabilizing the microbial communities. Synthetic peptides have also been marked as a potential solution to help combat antibiotic-resistant microbes such as drug-resistant Staphylococcus aureus. They can also act intracellularly – for instance, on protein biosynthesis or DNA replication .
As well as mimicking pharmacological properties, structural and amino acid sequence improvements can also be used to address challenges associated with natural AMPs, such as instability when used as a drug, host toxicity, rapid degradation by proteases and loss of activity in presence of serum and high salt concentrations [2,3]. Short-sequence AMPs (<20 amino acids) can be used to combine optimal antimicrobial activity with inexpensive chemical synthesis and modifications required to ensure stability, low toxicity and microbial specificity, and are compatible with large-scale production .
1. Sinha, R. & Dhukla, P. Antimicrobial Peptides: Recent Insights on Biotechnological Interventions and Future Perspectives. Protein & Peptide Letters 26, 79-87 (2019).
2. Chen, C. H. & Lu, T. Development and Challenges of Antimicrobial Peptides for Therapeutic Applications. Antibiotics 10.3390/antibiotics9010024 (2020).
3. Vanzolini, T. et al. Multitalented synthetic antimicrobial peptides and their antibacterial, antifungal and antiviral mechanisms. Int. J. Mol. Sci. 23, 545 (2022).
4. Rahnamaeian, M. & Vileinskas, A. Short antimicrobial peptides as cosmetic ingredients to deter dermatological pathogens. Appl. Microbiol. Biotechnol. 99, 8847–8855 (2015).
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