Design and Synthesis of an RGD Peptidomimetic-Paclitaxel Conjugate Targeting αvβ3 Integrin for Tumour-Directed Drug Delivery

A 1,2,3-triazole-based RGD peptidomimetic having nanomolar affinity for αvβ3 integrin was conjugated to the potent antimitotic paclitaxel via an oxime heterobifunctional linker. The resulting construct maintained nanomolar binding concentration to αvβ3 integrin and showed 11-fold selectivity in terms of cytotoxicity towards highly αvβ3 expressing U87MG cancer cells relative to non αvβ3 expressing MCF7 cells, indicating promising cancer cell targeting capacity. 1 Design 2 Retrosynthesis 3 Synthesis 4 Solid-Phase Receptor Binding Assay 5 Cell Cytotoxicity Assays 6 Metabolic Stability Assays 7 Conclusions