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Anticancer Gold(III) Porphyrins Target Mitochondrial Chaperone Hsp60

Hu, Di ; Liu, Yungen ; Lai, Yau-Tsz ; Tong, Ka-Chung ; Fung, Yi-Man ; Lok, Chun-Nam ; Che, Chi-Ming

Angewandte Chemie, 2016-01, Vol.128 (4), p.1409-1413 [Periódico revisado por pares]

Weinheim: Blackwell Publishing Ltd

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Título:
Anticancer Gold(III) Porphyrins Target Mitochondrial Chaperone Hsp60
Autor: Hu, Di ; Liu, Yungen ; Lai, Yau-Tsz ; Tong, Ka-Chung ; Fung, Yi-Man ; Lok, Chun-Nam ; Che, Chi-Ming
Assuntos: Affinity ; Affinity labelling ; Anticancer properties ; Assaying ; Biological ; Biologische Zielstrukturen ; Biology ; Cancer ; Cellular ; Chemical synthesis ; Chemische Proteomik ; Chemistry ; Coordination compounds ; Fluorescence ; Gold ; Goldporphyrine ; Heat ; Heat exchange ; Hsp60 ; Hsp60 protein ; Inhibition ; Labels ; Ligands ; Marking ; Metal complexes ; Metals ; Mitochondria ; Molecular structure ; NMR ; Nuclear magnetic resonance ; Panels ; Physiology ; Porphyrins ; Proteins ; Proteomics ; Quenching ; Reduction ; Reduction (metal working) ; Saturation ; Stability ; Synthesis (chemistry) ; Target recognition ; Tumortherapeutika
É parte de: Angewandte Chemie, 2016-01, Vol.128 (4), p.1409-1413
Notas: istex:8EE0EDA12DE986AE0AD0AEC4DA799CEAADA40D96
ArticleID:ANGE201509612
ark:/67375/WNG-J0H0493N-X
These authors contributed equally to this work.
ObjectType-Article-1
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Descrição: Identification of the molecular target(s) of anticancer metal complexes is a formidable challenge since most of them are unstable toward ligand exchange reaction(s) or biological reduction under physiological conditions. Gold(III) meso‐tetraphenylporphyrin (gold‐1 a) is notable for its high stability in biological milieux and potent in vitro and in vivo anticancer activities. Herein, extensive chemical biology approaches employing photo‐affinity labeling, click chemistry, chemical proteomics, cellular thermal shift, saturation‐transfer difference NMR, protein fluorescence quenching, and protein chaperone assays were used to provide compelling evidence that heat‐shock protein 60 (Hsp60), a mitochondrial chaperone and potential anticancer target, is a direct target of gold‐1 a in vitro and in cells. Structure–activity studies with a panel of non‐porphyrin gold(III) complexes and other metalloporphyrins revealed that Hsp60 inhibition is specifically dependent on both the gold(III) ion and the porphyrin ligand. Eine Schwäche für Gold hat das Hitzeschockprotein Hsp60, denn es ist ein direktes molekulares Ziel der Antitumorverbindung Gold(III)‐meso‐tetraphenylporphyrin (Gold‐1 a) unter In‐vitro‐ ebenso wie unter zellulären Bedingungen. Dies ergaben chemisch‐biologische Studien, bei denen unter anderem Photoaffinitätsmarkierung, Klick‐Chemie, chemische Proteomik und NMR‐Spektroskopie zum Einsatz kamen.
Editor: Weinheim: Blackwell Publishing Ltd
Idioma: Inglês;Alemão

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Anticancer Gold(III) Porphyrins Target Mitochondrial Chaperone Hsp60

Hu, Di ; Liu, Yungen ; Lai, Yau-Tsz ; Tong, Ka-Chung ; Fung, Yi-Man ; Lok, Chun-Nam ; Che, Chi-Ming

Weinheim: Blackwell Publishing Ltd

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