Enhanced antimicrobial activity of novel synthetic peptides derived from vejovine and hadrurin

Background: Microbial antibiotic resistance is a challenging medical problem nowadays. Two scorpion peptides displaying antibiotic activity: hadrurin and vejovine were taken as models for the design of novel shorter peptides with similar activity. Methods: Using the standard Fmoc-based solid phase synthesis technique of Merrifield twelve peptides (18 to 29 amino acids long) were synthesized, purified and assayed against a variety of multi-drug resistant Gram-negative bacteria from clinical isolates. Hemolytic and antiparasitic activities of the peptides and their possible interactions with eukaryotic cells were verified. Release of the fluorophore calcein from liposomes treated with these peptides was measured. Results: A peptide with sequence GILKTIKSIASKVANTVQKLKRKAKNAVA), and three analogs: Delta(A29), Delta(K12-Q18; N26-A29), and K4N Delta(K12'-Q18; N26-A29) were shown to inhibit the growth of Gram-negative (E. coli ATCC25922) and Gram-positive bacteria (S. aureus), as well as multi-drug resistant (MDR) clinical isolated. The antibacterial and antiparasitic activities were found with peptides at 0.78 to 25 mu M and 5 to 25 mu M concentration, respectively. These peptides have low cytotoxic and hemolytic activities at concentrations significantly exceeding their minimum inhibitory concentrations (MICs), showing values between 40 and 900 mu M for their EC50, compared to the parent peptides vejovine and hadrurin that at the same concentration of their MICs lysed more than 50% of human erythrocytes cells. Conclusions: These peptides promise to be good candidates to combat infections caused by Gram-negative bacteria from nosocomial infections. General significance: Our results confirm that well designed synthetic peptides can be an alternative for solving the lack of effective antibiotics to control bacterial infections. (C) 2013 Elsevier B.V. All rights reserved.