Enhanced Antimicrobial Activity of AamAP1-Lysine, a Novel Synthetic Peptide Analog Derived from the Scorpion Venom Peptide AamAP1

Pharmaceuticals

Ammar Almaaytah⁴  Shadi Tarazi³  Ahmad Abu-Alhaijaa³  Yara Altall⁴  Nizar Alshar’i²  Khaldon Bodoor¹ 

[1]Department of Biotechnology and Genetic Engineering, Faculty of Science and Arts, Jordan University of Science and Technology, P.O. Box 3030, Irbid 22110, Jordan

[2] E-Mail:

[3]Department of Medicinal Chemistry, Faculty of Pharmacy, Jordan University of Science and Technology, P.O. Box 3030, Irbid 22110, Jordan

[4] E-Mails:

[5]Department of Applied Biological Sciences, Faculty of Science and Arts, Jordan University of Science and Technology, P.O. Box 3030, Irbid 22110, Jordan

[6] E-Mails:

[7]Department of Pharmaceutical Technology, Faculty of Pharmacy, Jordan University of Science and Technology, P.O. Box 3030, Irbid 22110, Jordan

[8] E-Mail:

关键词: antimicrobial peptides;    peptide design;    membrane-permeation;    scorpion peptide;    molecular modeling;   

DOI  :  10.3390/ph7050502

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.