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).