Cellular Uptake and Photo-Cytotoxicity of a Gadolinium(III)-DOTA-Naphthalimide Complex “Clicked” to a Lipidated Tat Peptide

A new bifunctional macrocyclic chelator featuring a conjugatable alkynyl-naphthalimide fluorophore pendant group has been prepared and its Gd(III) complex coupled to a cell-penetrating lipidated azido-Tat peptide derivative using Cu(I)-catalysed “click” chemistry. The resulting fluorescent conjugate...

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Autores principales: O’Malley, William I., Rubbiani, Riccardo, Aulsebrook, Margaret L., Grace, Michael R., Spiccia, Leone, Tuck, Kellie L., Gasser, Gilles, Graham, Bim
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6273236/
https://www.ncbi.nlm.nih.gov/pubmed/26861271
http://dx.doi.org/10.3390/molecules21020194
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author O’Malley, William I.
Rubbiani, Riccardo
Aulsebrook, Margaret L.
Grace, Michael R.
Spiccia, Leone
Tuck, Kellie L.
Gasser, Gilles
Graham, Bim
author_facet O’Malley, William I.
Rubbiani, Riccardo
Aulsebrook, Margaret L.
Grace, Michael R.
Spiccia, Leone
Tuck, Kellie L.
Gasser, Gilles
Graham, Bim
author_sort O’Malley, William I.
collection PubMed
description A new bifunctional macrocyclic chelator featuring a conjugatable alkynyl-naphthalimide fluorophore pendant group has been prepared and its Gd(III) complex coupled to a cell-penetrating lipidated azido-Tat peptide derivative using Cu(I)-catalysed “click” chemistry. The resulting fluorescent conjugate is able to enter CAL-33 tongue squamous carcinoma cells, as revealed by confocal microscopy, producing a very modest anti-proliferative effect (IC(50) = 93 µM). Due to the photo-reactivity of the naphthalimide moiety, however, the conjugate’s cytotoxicity is significantly enhanced (IC(50) = 16 µM) upon brief low-power UV-A irradiation.
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spelling pubmed-62732362018-12-28 Cellular Uptake and Photo-Cytotoxicity of a Gadolinium(III)-DOTA-Naphthalimide Complex “Clicked” to a Lipidated Tat Peptide O’Malley, William I. Rubbiani, Riccardo Aulsebrook, Margaret L. Grace, Michael R. Spiccia, Leone Tuck, Kellie L. Gasser, Gilles Graham, Bim Molecules Article A new bifunctional macrocyclic chelator featuring a conjugatable alkynyl-naphthalimide fluorophore pendant group has been prepared and its Gd(III) complex coupled to a cell-penetrating lipidated azido-Tat peptide derivative using Cu(I)-catalysed “click” chemistry. The resulting fluorescent conjugate is able to enter CAL-33 tongue squamous carcinoma cells, as revealed by confocal microscopy, producing a very modest anti-proliferative effect (IC(50) = 93 µM). Due to the photo-reactivity of the naphthalimide moiety, however, the conjugate’s cytotoxicity is significantly enhanced (IC(50) = 16 µM) upon brief low-power UV-A irradiation. MDPI 2016-02-05 /pmc/articles/PMC6273236/ /pubmed/26861271 http://dx.doi.org/10.3390/molecules21020194 Text en © 2016 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons by Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
O’Malley, William I.
Rubbiani, Riccardo
Aulsebrook, Margaret L.
Grace, Michael R.
Spiccia, Leone
Tuck, Kellie L.
Gasser, Gilles
Graham, Bim
Cellular Uptake and Photo-Cytotoxicity of a Gadolinium(III)-DOTA-Naphthalimide Complex “Clicked” to a Lipidated Tat Peptide
title Cellular Uptake and Photo-Cytotoxicity of a Gadolinium(III)-DOTA-Naphthalimide Complex “Clicked” to a Lipidated Tat Peptide
title_full Cellular Uptake and Photo-Cytotoxicity of a Gadolinium(III)-DOTA-Naphthalimide Complex “Clicked” to a Lipidated Tat Peptide
title_fullStr Cellular Uptake and Photo-Cytotoxicity of a Gadolinium(III)-DOTA-Naphthalimide Complex “Clicked” to a Lipidated Tat Peptide
title_full_unstemmed Cellular Uptake and Photo-Cytotoxicity of a Gadolinium(III)-DOTA-Naphthalimide Complex “Clicked” to a Lipidated Tat Peptide
title_short Cellular Uptake and Photo-Cytotoxicity of a Gadolinium(III)-DOTA-Naphthalimide Complex “Clicked” to a Lipidated Tat Peptide
title_sort cellular uptake and photo-cytotoxicity of a gadolinium(iii)-dota-naphthalimide complex “clicked” to a lipidated tat peptide
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6273236/
https://www.ncbi.nlm.nih.gov/pubmed/26861271
http://dx.doi.org/10.3390/molecules21020194
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