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Design and synthesis of an RGD peptidomimetic-paclitaxel conjugate targeting αvβ3 integrin for tumour-directed drug delivery

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journal contribution
posted on 2019-01-15, 09:07 authored by Monica Piras, Alexandra Andriu, Andrea Testa, Paul Wienecke, Ian N. Fleming, Matteo Zanda
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.

Funding

We thank the Development Trust, University of Aberdeen, for funding a fellowship to M.P. and a studentship to A.A.

History

School

  • Science

Department

  • Chemistry

Published in

Synlett

Volume

28

Issue

20

Pages

2769 - 2776

Citation

PIRAS, M. ... et al, 2017. Design and synthesis of an RGD peptidomimetic-paclitaxel conjugate targeting αvβ3 integrin for tumour-directed drug delivery. Synlett, 28 (20), pp.2769-2776.

Publisher

© Georg Thieme Verlag

Version

  • AM (Accepted Manuscript)

Publisher statement

This work is made available according to the conditions of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) licence. Full details of this licence are available at: https://creativecommons.org/licenses/by-nc-nd/4.0/

Acceptance date

2017-08-07

Publication date

2017-09-01

Notes

This paper was published in the journal Synlett and the definitive published version is available at https://www.thieme-connect.de/products/ejournals/abstract/10.1055/s-0036-1590898.

ISSN

0936-5214

eISSN

1437-2096

Language

  • en