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 α v β 3 integrin was conjugated to the potent antimitotic paclitaxel via an oxime heterobifunctional linker. The resulting construct maintained nanomolar binding concentration to α v β 3 integrin and showed 11-fold selectivity in terms of cytotoxicity towards highly α v β 3 expressing U87MG cancer cells relative to non α v β 3 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.