Novel peptidomimetics: synthesis, characterization, and molecular modeling studies

Since PD-1/PD-L1 plays a crucial role as immune checkpoint molecules in many cancers, developing immunotherapy with peptidomimetics that block these molecules is an important option in anticancer therapy. In this study, several peptidomimetic compounds were screened from the literature using computational methods, and it was determined that 2-amino-benzothiazole-based peptidomimetics show affinity for the active site of PD-L1. In the light of molecular modelling studies, six molecules with free binding energies ranging from -6.7 to -7.2 kcal/mol were chosen from the library of 2-amino-benzothiazole-based peptidomimetics for synthesis. These synthesized six compounds were characterized with 1H-NMR, 13C-NMR, FTIR and HRMS. Molecular modelling studies showed that these novel 2-amino-benzothiazole-based peptidomimetics may be potential checkpoint inhibitors for cancer immunotherapy.