Design and Synthesis of an RGD Peptidomimetic-Paclitaxel Conjugate Targeting αvβ3 Integrin for Tumour-Directed Drug DeliveryWe thank the Development Trust, University of Aberdeen, for funding a fellowship to M.P. and a studentship to A.A.
Received: 16 June 2017
Accepted after revision: 07 August 2017
01 September 2017 (eFirst)
This article is dedicated to Professor Victor Snieckus on the occasion of his 80th birthday
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.
4 Solid-Phase Receptor Binding Assay
5 Cell Cytotoxicity Assays
6 Metabolic Stability Assays