Targeted cell imaging properties of a deep red luminescent iridium(III) complex conjugated with a c-Myc signal peptide

Day, Adam H., Ubler, Martin H., Best, Hannah L., Lloyd-Evans, Emyr, Mart, Robert J., Fallis, Ian A., Allemann, Rudolf K., Al-Wattar, Eman A. H., Keymer, Nathaniel I., Buurma, Niklaas J. and Pope, Simon J. A. 2020. Targeted cell imaging properties of a deep red luminescent iridium(III) complex conjugated with a c-Myc signal peptide. Chemical Science 11 (6) , pp. 1599-1606. 10.1039/C9SC05568A

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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
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:	15 Oct 2020 01:35
URI:	http://orca.cf.ac.uk/id/eprint/128838

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