biostudies-literatureKim SKorea Health Industry Development InstituteNational Research Foundation of Korea387-393https://www.ebi.ac.uk/biostudies/studies/S-EPMC11740091biostudies-literatureUnknown6(3)Antibody-recruiting molecules (ARMs) have emerged as a promising strategy for enhancing immune responses against pathogens and cancer cells. In this study, we developed a novel class of antibacterial ARMs utilizing siderophores, small iron-chelating compounds, as targeting motifs. Siderophores naturally exhibit high specificity for bacterial pathogens due to their role in iron acquisition, making them ideal candidates for selective targeting. We identified a potent ARM, GNP3, comprising MECAM, a siderophore mimetic, and 2,4-dinitrophenyl (DNP), a motif recognized by endogenous antibodies, connected <i>via</i> a flexible linker. GNP3 binds simultaneously to both anti-DNP antibody and the siderophore receptor, FepA, facilitating the targeted deposition of antibodies on the surface of FepA-exRSC chemical biologySiderophore-based targeted antibody recruitment for promoting immune responses towards Gram-negative pathogens.PMC11740091HR22C1734NRF-2021R1A2C1094331RS-2023-00259824Kim SKim DHPark HSKim DYChoi CHOh JKim HJKang MJJoh HfalseSiderophore-based targeted antibody recruitment for promoting immune responses towards Gram-negative pathogens.Antibody-recruiting molecules (ARMs) have emerged as a promising strategy for enhancing immune responses against pathogens and cancer cells. In this study, we developed a novel class of antibacterial ARMs utilizing siderophores, small iron-chelating compounds, as targeting motifs. Siderophores naturally exhibit high specificity for bacterial pathogens due to their role in iron acquisition, making them ideal candidates for selective targeting. We identified a potent ARM, GNP3, comprising MECAM, a siderophore mimetic, and 2,4-dinitrophenyl (DNP), a motif recognized by endogenous antibodies, connected <i>via</i> a flexible linker. GNP3 binds simultaneously to both anti-DNP antibody and the siderophore receptor, FepA, facilitating the targeted deposition of antibodies on the surface of FepA-ex2025-01-01T00:00:00Z2025 Mar2025-04-04T13:46:52.854Z2025-04-04T13:46:52.854ZS-EPMC117400913983068410.1039/d4cb00293h