FMO
Safety and efficacy are important in precision medicine. An attractive strategy to maximize these areas is using LTDs, which typically comprise a targeting ligand, spacer, cleavable linker, and therapeutic payload.23 Because LTDs can achieve the required therapeutic potency with minimal toxicity, the successful design of each component and an appropriate delivery mechanism remain active areas of research.89-92 In the present study, we used the FMO utility in GridMol version 2.0 combined with TS theory to elucidate the releasing mechanism of a drug conjugate with a triple payload of paclitaxel. We focused only on the initial step (breaking the spacer–linker bond) in the drug-release process (Figure 15). First, the chemical structure of the ligand-AB3 dendritic-prodrug conjugate (Figure 16) was prepared using the molecule-building module of GridMol. Seven components corresponded to four function types (i.e., targeting ligand, spacer, linker, and drug) (Figure 16).