Abstract: There is great interest in the development of antimicrobial peptides as a potentially novel class of antimicrobial agents. Several structural determinants are responsible for the antimicrobial and cytolytic activity of antimicrobial peptides. In our study, a new synthetic peptide analog, AamAP1-Lysine from the naturally occurring scorpion venom antimicrobial peptide AamAP1, was designed by modifying the parent peptide in order to increase the positive charge and optimize other physico-chemical parameters involved in antimicrobial activity. AamAP1-Lysine displayed potent antibacterial activity against Gram-positive and Gram-negative bacteria. The minimum inhibitory concentration was in the range of 5 to 15 µM with a 10 fold increase in potency over the parent peptide. The hemolytic and antiproliferative activity of AamAP1-Lysine against eukaryotic mammalian cells was minimal at the concentration range needed to inhibit bacterial growth. The antibacterial mechanism analysis indicated that AamAP1-Lysine is probably inducing bacterial cell death through membrane damage and permeabilization determined by the release of β-galactosidase enzyme from peptide treated E. coli cells. DNA binding studies revealed that AamAP1-Lysine caused complete retardation of DNA migration and could display intracellular activities in addition to the membrane permeabilization mode of action reported earlier. In conclusion, AamAP1-Lysine could prove to be a potential candidate for antimicrobial drug development in future studies.
Keywords: antimicrobial peptides; peptide design; membrane-permeation; scorpion peptide; molecular modeling
Export to BibTeX
MDPI and ACS Style
Almaaytah, A.; Tarazi, S.; Abu-Alhaijaa, A.; Altall, Y.; Alshar'i, N.; Bodoor, K.; Al-Balas, Q. Enhanced Antimicrobial Activity of AamAP1-Lysine, a Novel Synthetic Peptide Analog Derived from the Scorpion Venom Peptide AamAP1. Pharmaceuticals 2014, 7, 502-516.
Almaaytah A, Tarazi S, Abu-Alhaijaa A, Altall Y, Alshar'i N, Bodoor K, Al-Balas Q. Enhanced Antimicrobial Activity of AamAP1-Lysine, a Novel Synthetic Peptide Analog Derived from the Scorpion Venom Peptide AamAP1. Pharmaceuticals. 2014; 7(5):502-516.
Almaaytah, Ammar; Tarazi, Shadi; Abu-Alhaijaa, Ahmad; Altall, Yara; Alshar'i, Nizar; Bodoor, Khaldon; Al-Balas, Qosay. 2014. "Enhanced Antimicrobial Activity of AamAP1-Lysine, a Novel Synthetic Peptide Analog Derived from the Scorpion Venom Peptide AamAP1." Pharmaceuticals 7, no. 5: 502-516.