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

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.