Combining naturally occurring peptides by hybridizing them with known active peptides to synthesize effective antimicrobial peptides with minimal cytotoxicity.

Antibiotic resistance is a significant concern that poses a potential risk of increased harm from future infectious diseases. Consequently, antimicrobial peptides (AMPs) are regarded as an alternative to antibiotics as they are less prone to bacterial resistance. However, AMPs often exhibit toxicity, instability, and substantial costs. Therefore, careful design choices will have to be considered to address these challenges. One major hurdle that still needs to be surmounted is AMPs potential toxicity to human cells.

To mitigate toxicity, a method has been developed that involves hybridization of peptides. This technique combines different segments of natural peptides to create hybridized AMPs (hAMPs). By leveraging the hybridization process, the antimicrobial properties of hAMPs are optimized while minimizing cytotoxicity.

The design of hAMPs utilizes VmCT1, an AMP derived from scorpion venom, as well as other established amphiphilic AMP templates. Hybridized amphiphilic molecules are synthesized for therapeutic screening through a combination of hydrophobic and hydrophilic moieties. Extensive testing evaluates these newly formed peptides' antimicrobial, antiplasmodial, and cytotoxic properties, enabling the identification of clinically relevant hAMPs.

• hAMPs derivatives exhibit lower toxicity than the parent peptides
• hAMPs show strong resistance to proteolytic degradation
• Two of the hAMPs showed stronger anti-infective properties in a mouse model than parent peptides