SYNLETT RGD-PTX-Zanda final unformatted (1).pdf (591.21 kB)
Design and synthesis of an RGD peptidomimetic-paclitaxel conjugate targeting αvβ3 integrin for tumour-directed drug delivery
journal contribution
posted on 2019-01-15, 09:07 authored by Monica Piras, Alexandra Andriu, Andrea Testa, Paul Wienecke, Ian N. Fleming, Matteo ZandaA 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
SynlettVolume
28Issue
20Pages
2769 - 2776Citation
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 VerlagVersion
- 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
2017-08-07Publication date
2017-09-01Notes
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
0936-5214eISSN
1437-2096Publisher version
Language
- en