Synlett
DOI: 10.1055/s-0036-1590898
letter
© Georg Thieme Verlag Stuttgart · New York

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

Monica Piras*a, Alexandra Andriua, Andrea Testaa, Paul Wieneckea, Ian N. Fleminga, Matteo Zanda*a, b
  • aInstitute of Medical Sciences and Kosterlitz Centre for Therapeutics, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, Scotland, UK   Email: m.zanda@abdn.ac.uk
  • bC.N.R. – I.C.R.M., via Mancinelli 7, 20131 Milan, Italy
We thank the Development Trust, University of Aberdeen, for funding a fellowship to M.P. and a studentship to A.A.
Further Information

Publication History

Received: 16 June 2017

Accepted after revision: 07 August 2017

Publication Date:
01 September 2017 (eFirst)

This article is dedicated to Professor Victor Snieckus on the occasion of his 80th birthday

Abstract

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

Supporting Information