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Enhanced Cytotoxicity through Conjugation of a "Clickable" Luminescent Re(I) Complex to a Cell-Penetrating Lipopeptide.

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" (99m)Tc 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)](BF 4 ), and cytotoxicity studies showed that this resulted in an increase in potency to a level comparable with cisplatin (13.0 ± 2.0 μM).

journal_name

ACS Med Chem Lett

journal_title

ACS medicinal chemistry letters

authors

Leonidova A,Pierroz V,Adams LA,Barlow N,Ferrari S,Graham B,Gasser G

doi

10.1021/ml500158w

subject

Has Abstract

pub_date

2014-05-15 00:00:00

pages

809-14

issue

7

issn

1948-5875

journal_volume

5

pub_type

杂志文章

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