Day, Adam H., Ubler, Martin H., Best, Hannah L., Lloyd-Evans, Emyr ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
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Abstract
A nuclear localisation sequence (NLS) peptide, PAAKRVKLD, derived from the human c-Myc regulator gene, has been functionalised with a long wavelength (λex = 550 nm; λem = 677 nm) cyclometalated organometallic iridium(III) complex to give the conjugate Ir-CMYC. Confocal fluorescence microscopy studies on human fibroblast cells imaged after 18–24 h incubation show that Ir-CMYC concentrations of 80–100 μM promote good cell uptake and nuclear localisation, which was confirmed though co-localisation studies using Hoechst 33342. In comparison, a structurally related, photophysically analogous iridium(III) complex lacking the peptide sequence, Ir-PYR, showed very different biological behaviour, with no evidence of nuclear, lysosomal or autophagic vesicle localisation and significantly increased toxicity to the cells at concentrations >10 μM that induced mitochondrial dysfunction. Supporting UV-visible and circular dichroism spectroscopic studies show that Ir-PYR and Ir-CMYC display similarly low affinities for DNA (ca. 103 M−1), consistent with electrostatic binding. Therefore the translocation and nuclear uptake properties of Ir-CMYC are attributed to the presence of the PAAKRVKLD nuclear localisation sequence in this complex.
Item Type: | Article |
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Date Type: | Publication |
Status: | Published |
Schools: | Biosciences Chemistry |
Publisher: | Royal Society of Chemistry |
ISSN: | 2041-6520 |
Funders: | BBSRC and Royal Society |
Date of First Compliant Deposit: | 20 January 2020 |
Date of Acceptance: | 14 December 2019 |
Last Modified: | 04 May 2024 01:10 |
URI: | https://orca.cardiff.ac.uk/id/eprint/128838 |
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