title: 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).
authors: Department of Chemistry, University of Zurich , Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
authors: Anna
authors: A
authors: Leonidova
authors: Department of Chemistry, University of Zurich , Winterthurerstrasse 190, CH-8057 Zurich, Switzerland ; Institute of Molecular Cancer Research , Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
authors: Vanessa
authors: V
authors: Pierroz
authors: Monash Institute of Pharmaceutical Sciences, Monash University , 381 Royal Parade, Parkville, Victoria 3052, Australia.
authors: Luke A
authors: LA
authors: Adams
authors: Monash Institute of Pharmaceutical Sciences, Monash University , 381 Royal Parade, Parkville, Victoria 3052, Australia.
authors: Nicholas
authors: N
authors: Barlow
authors: Institute of Molecular Cancer Research , Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
authors: Stefano
authors: S
authors: Ferrari
authors: Monash Institute of Pharmaceutical Sciences, Monash University , 381 Royal Parade, Parkville, Victoria 3052, Australia.
authors: Bim
authors: B
authors: Graham
authors: Department of Chemistry, University of Zurich , Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
authors: Gilles
authors: G
authors: Gasser
keywords: Anticancer; fluorescence microscopy; medicinal organometallic chemistry; peptide; rhenium complexes