Enhanced cytotoxicity through conjugation of a "clickable" luminescent Re(I) complex to a cell-penetrating lipopeptide

Anna Leonidova, Vanessa Pierroz, Luke Anthony Adams, Nicholas Barlow, Stefano Ferrari, Bimbil Graham, Gilles Albert Gasser

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Abstract

Re(I) tricarbonyl polypyridine-based complexes are particularly attractive metal complexes in the field of inorganic chemical biology due to their luminescent properties, ease of conjugation to targeting biomolecules, and the possibility to prepare their hot 99mTc analogues for radioimaging. In this study, we prepared and characterized a novel, clickable complex, [Re(2,2 -bipyridine)(3-ethynylpyridine)(CO) 3](BF4) ([Re(CO)3(bipy)(py-alkyne)](BF 4)), exhibiting the characteristic luminescent properties and moderate cytotoxicity of this general class of compound. Using Cu(I)-catalyzed click chemistry, the complex was efficiently attached to a lipidated peptide known to increase cell permeability, namely, the myristoylated HIV-1 Tat peptide (myr-Tat), to give Re-myr-Tat. Fluorescence microscopy localization in human cervical cancer cells (HeLa) confirmed enhanced cellular uptake of Re-myr-Tat compared with [Re(CO)3(bipy)(py-alkyne)](BF4), and cytotoxicity studies showed that this resulted in an increase in potency to a level comparable with cisplatin (13.0 ? 2.0 ?M).
Original languageEnglish
Pages (from-to)809 - 814
Number of pages6
JournalACS Medicinal Chemistry Letters
Volume5
Issue number7
DOIs
Publication statusPublished - 2014

Cite this

Leonidova, Anna ; Pierroz, Vanessa ; Adams, Luke Anthony ; Barlow, Nicholas ; Ferrari, Stefano ; Graham, Bimbil ; Gasser, Gilles Albert. / Enhanced cytotoxicity through conjugation of a "clickable" luminescent Re(I) complex to a cell-penetrating lipopeptide. In: ACS Medicinal Chemistry Letters. 2014 ; Vol. 5, No. 7. pp. 809 - 814.
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abstract = "Re(I) tricarbonyl polypyridine-based complexes are particularly attractive metal complexes in the field of inorganic chemical biology due to their luminescent properties, ease of conjugation to targeting biomolecules, and the possibility to prepare their hot 99mTc analogues for radioimaging. In this study, we prepared and characterized a novel, clickable complex, [Re(2,2 -bipyridine)(3-ethynylpyridine)(CO) 3](BF4) ([Re(CO)3(bipy)(py-alkyne)](BF 4)), exhibiting the characteristic luminescent properties and moderate cytotoxicity of this general class of compound. Using Cu(I)-catalyzed click chemistry, the complex was efficiently attached to a lipidated peptide known to increase cell permeability, namely, the myristoylated HIV-1 Tat peptide (myr-Tat), to give Re-myr-Tat. Fluorescence microscopy localization in human cervical cancer cells (HeLa) confirmed enhanced cellular uptake of Re-myr-Tat compared with [Re(CO)3(bipy)(py-alkyne)](BF4), and cytotoxicity studies showed that this resulted in an increase in potency to a level comparable with cisplatin (13.0 ? 2.0 ?M).",
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Enhanced cytotoxicity through conjugation of a "clickable" luminescent Re(I) complex to a cell-penetrating lipopeptide. / Leonidova, Anna; Pierroz, Vanessa; Adams, Luke Anthony; Barlow, Nicholas; Ferrari, Stefano; Graham, Bimbil; Gasser, Gilles Albert.

In: ACS Medicinal Chemistry Letters, Vol. 5, No. 7, 2014, p. 809 - 814.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Leonidova, Anna

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AU - Ferrari, Stefano

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AU - Gasser, Gilles Albert

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AB - Re(I) tricarbonyl polypyridine-based complexes are particularly attractive metal complexes in the field of inorganic chemical biology due to their luminescent properties, ease of conjugation to targeting biomolecules, and the possibility to prepare their hot 99mTc analogues for radioimaging. In this study, we prepared and characterized a novel, clickable complex, [Re(2,2 -bipyridine)(3-ethynylpyridine)(CO) 3](BF4) ([Re(CO)3(bipy)(py-alkyne)](BF 4)), exhibiting the characteristic luminescent properties and moderate cytotoxicity of this general class of compound. Using Cu(I)-catalyzed click chemistry, the complex was efficiently attached to a lipidated peptide known to increase cell permeability, namely, the myristoylated HIV-1 Tat peptide (myr-Tat), to give Re-myr-Tat. Fluorescence microscopy localization in human cervical cancer cells (HeLa) confirmed enhanced cellular uptake of Re-myr-Tat compared with [Re(CO)3(bipy)(py-alkyne)](BF4), and cytotoxicity studies showed that this resulted in an increase in potency to a level comparable with cisplatin (13.0 ? 2.0 ?M).

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