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 ORCID: https://orcid.org/0000-0002-3626-1611, Mart, Robert J. ORCID: https://orcid.org/0000-0003-2196-5840, Fallis, Ian A. ORCID: https://orcid.org/0000-0001-7361-0182, Allemann, Rudolf K. ORCID: https://orcid.org/0000-0002-1323-8830, Al-Wattar, Eman A. H., Keymer, Nathaniel I., Buurma, Niklaas J. ORCID: https://orcid.org/0000-0003-0260-5057 and Pope, Simon J. A. ORCID: https://orcid.org/0000-0001-9110-9711 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:	04 May 2024 01:10
URI:	https://orca.cardiff.ac.uk/id/eprint/128838

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