Anticancer Gold(III) Porphyrins Target Mitochondrial Chaperone Hsp60.
Angew Chem Int Ed Engl
; 55(4): 1387-91, 2016 Jan 22.
Article
em En
| MEDLINE
| ID: mdl-26663758
ABSTRACT
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 inâ
vitro and inâ
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 proteinâ
60 (Hsp60), a mitochondrial chaperone and potential anticancer target, is a direct target of gold-1 a inâ
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Porfirinas
/
Chaperonina 60
/
Ouro
/
Mitocôndrias
/
Antineoplásicos
Limite:
Humans
Idioma:
En
Revista:
Angew Chem Int Ed Engl
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Hong Kong