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

被引:41
作者
Almaaytah, Ammar [1 ]
Tarazi, Shadi [2 ]
Abu-Alhaijaa, Ahmad [2 ]
Altall, Yara [1 ]
Alshar'i, Nizar [3 ]
Bodoor, Khaldon [4 ]
Al-Balas, Qosay [3 ]
机构
[1] Jordan Univ Sci & Technol, Fac Pharm, Dept Pharmaceut Technol, POB 3030, Irbid 22110, Jordan
[2] Jordan Univ Sci & Technol, Fac Sci & Arts, Dept Appl Biol Sci, Irbid 22110, Jordan
[3] Jordan Univ Sci & Technol, Dept Med Chem, Fac Pharm, Irbid 22110, Jordan
[4] Jordan Univ Sci & Technol, Dept Biotechnol & Genet Engn, Fac Sci & Arts, Irbid 22110, Jordan
关键词
antimicrobial peptides; peptide design; membrane-permeation; scorpion peptide; molecular modeling;
D O I
10.3390/ph7050502
中图分类号
R914 [药物化学];
学科分类号
100701 ;
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 mu M 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 beta-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.
引用
收藏
页码:502 / 516
页数:15
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