Wu, Chih-LungChih-LungWuPeng, Kuang-LiKuang-LiPengBak-Sau YipChih, Ya-HanYa-HanChihCheng, Jya-WeiJya-WeiCheng2024-11-022024-11-022021https://scholars.lib.ntu.edu.tw/handle/123456789/722683The global spread of antibiotic-resistant infections has meant that there is an urgent need to develop new antimicrobial alternatives. In this study, we developed a strategy to boost and/or synergize the activity of conventional antibiotics by combination with antimicrobial peptides tagged with the bulky non-natural amino acid β-naphthylalanine (Nal) to their N- or C-terminus. A checkerboard method was used to evaluate synergistic effects of the parent peptide and the Nal-tagged peptides. Moreover, boron-dipyrro-methene labeled vancomycin was used to characterize the synergistic mechanism of action between the peptides and vancomycin on the bacterial strains. These Nal-tagged antimicrobial peptides also reduced the antibiotic-induced release of lipopolysaccharide from Gram-negative bacteria by more than 99.95%. Our results demonstrate that Nal-tagged peptides could help in developing antimicrobial peptides that not only have enhanced antibacterial activities but also increase the synergistic effects with conventional antibiotics against antibiotic-resistant bacteria.enend-taggingantibiotic resistanceantimicrobial peptides (AMP)bulky non-natural amino acidsynergism[SDGs]SDG3journal article10.3389/fmicb.2021.74776034733262