Tre-DNP

Tre-DNP is a first-generation antibody-recruiting small molecule (ARM) designed as a host-directed immunotherapy for mycobacterial infections. It consists of a trehalose targeting moiety covalently conjugated to a dinitrophenyl (DNP) hapten. Tre-DNP exploits the conserved trehalose monomycolate metabolic pathway of mycobacteria, serving as a substrate for extracellular antigen 85 (Ag85) mycolyltransferases. This allows the molecule to be metabolically incorporated into the outer-membrane glycolipids of mycobacterial species, including Mycobacterium tuberculosis, Mycobacterium abscessus, Mycobacterium avium, and Mycobacterium smegmatis. Once integrated, the surface-exposed DNP hapten recruits endogenous anti-DNP antibodies, flagging the bacteria for opsonization. This antibody recruitment triggers Fcγ receptor (FcγR)-mediated phagocytosis and enhances intracellular killing by macrophages through increased phagosome-lysosome fusion and reactive oxygen species (ROS) production.

Other names

Tre-DNP ARMtrehalose-DNP conjugatetrehalose-dinitrophenyltrehalose-dinitrophenyl conjugate