Enhancement of the activity of scorpion short-chain antimicrobial peptides by addition of basic residues at the C-terminus.

Scorpion venom contains antimicrobial peptides (AMPs). These AMPs are classified into three families based on peptide length: long-chain (>35 residues), intermediate-chain (20-35 residues), and short-chain (13-19 residues) AMPs. Previously, we identified both short- and intermediate-chain AMPs from the venom of the scorpion Isometrus maculatus. A comparative analysis of their antibacterial activities revealed that short-chain AMPs exhibit relatively weaker activity than intermediate-chain AMPs. A structural comparison indicated that intermediate-chain AMPs possess a longer C-terminal region enriched in basic residues, a feature absent in short-chain AMPs. Removal of this C-terminal basic region from intermediate-chain AMPs resulted in a marked loss of antibacterial activity. Conversely, the addition of basic residues at the C-termini of short-chain AMPs significantly enhanced their activity. These results demonstrate that basic residues in the C-terminal region of scorpion intermediate-chain AMPs are crucial for antibacterial activity.