Introduction: The rise in global bacterial resistance necessitates the discovery of novel antibiotics. Plant-derived Antimicrobial Peptides (AMPs) offer structural diversity and biocompatibility. This study aims to investigate the green synthesis and biological activities of derivatives of NCBP, a linear non-classical AMP identified from plants. Methods: Five NCBP derivatives (NCBP-1 to NCBP-5) were generated using a green tag-assisted peptide synthesis (TAPS) strategy, combined with site-directed mutagenesis and terminal modification. The peptides were characterized by MS and HPLC and subsequently evaluated for antibacterial activity against ten bacterial strains, salt tolerance, and cytotoxicity in Results: NCBP-1 was identified as the lead derivative, demonstrating potent antibacterial activity (MIC 8 μg·mL⁸¹) and low cytotoxicity. It also exhibited moderate anti-inflammatory activity in LPSstimulated RAW 264.7 macrophages. Its antibacterial mechanism was further supported by favorable molecular docking interactions with E. coli outer membrane LPS (PDB ID: 4RHB). Discussion: The combined approach successfully identified NCBP-1 as a potent antibacterial candidate. Its activity against Gram-negative bacteria is likely related to LPS binding, as suggested by the docking results. Further studies would be needed to fully elucidate its mechanism of action. Conclusion: NCBP-1 represents a promising lead for the development of novel antibacterial agents, particularly for treating Gram-negative bacterial infections.
Geng et al. (Sun,) studied this question.