Design, synthesis, and antimicrobial activities of novel functional peptides against Gram-positive and Gram-negative...

The extensive use of antibiotics in medicine results in the multidrug resistance of bacteria, making the development of new antimicrobial agents an urgent need. Antimicrobial peptides (AMPs) are considered as a new class of antibiotic with characteristics including an ability to kill target cells rapidly and a broad spectrum of activity. We have developed a potent antimicrobial peptide MAP-0403 (MIC = 5 μM), but it exhibited a high hemolytic side-effect (70.7%). To reduce its hemolytic effect and increase antimicrobial activity, three peptides derivatives of MAP-0403 (J-1, J-2, and J-3) were designed, synthesized by solid phase synthesis, purified by RP-HPLC, and characterized by MALDI-TOF MS. Structure-activity relationships of these peptides were studied by using circular dichroism and antimicrobial assays. The percentage of helical structure in J-1, J-2, and J-3 was lower than that of MAP-0403. The antimicrobial activity of J-1 was the same as that of MAP-0403 (MIC = 5 μM), J-2 exhibited the highest activity (MIC = 2.5 μM), while J-3 showed decreased activity (MIC = 10 μM). Compared to MAP-0403, J-2 showed significantly reduced hemolytic effect (3.4%), while J-1 and J-3 showed slightly decreased hemolytic effect (46.2%, 55.6%, respectively). Peptide J-2 was discovered as a novel and potent antimicrobial agents.