Repository logo

Infoscience

  • English
  • French
Log In
Logo EPFL, École polytechnique fédérale de Lausanne

Infoscience

  • English
  • French
Log In
  1. Home
  2. Academic and Research Output
  3. Journal articles
  4. X-ray absorption spectroscopy studies of the adducts formed between cytotoxic gold compounds and two major serum proteins
 
research article

X-ray absorption spectroscopy studies of the adducts formed between cytotoxic gold compounds and two major serum proteins

Messori, L.
•
Balerna, A.
•
Ascone, I.
Show more
2011
Journal of Biological Inorganic Chemistry

Gold metallodrugs form a class of promising antiproliferative agents showing a high propensity to react with proteins. We exploit here X-ray absorption spectroscopy (XAS) methods [both X-ray absorption near-edge spectroscopy (XANES) and extended X-ray absorption fine structure (EXAFS)] to gain insight into the nature of the adducts formed between three representative gold(I, III) metallodrugs (i.e., auranofin, Au(2,2'-bipyridine)(OH)(2), Aubipy, and dinuclear Au-2(6,6'-dimethyl-2,2'-bipyridine)(2)(mu-O)(2)(2), Auoxo6) and two major plasma proteins, namely, bovine serum albumin (BSA) and human serum apotransferrin (apoTf). The following metallodrug-protein systems were investigated in depth: auranofin/apoTf, Aubipy/BSA, and Auoxo6/apoTf. XANES spectra revealed that auranofin, upon protein binding, conserves its gold(I) oxidation state. Protein binding most probably takes place through release of the thiosugar ligand and its subsequent replacement by a thiol (or a thioether) from the protein. This hypothesis is independently supported by EXAFS results. In contrast, the reactions of Aubipy with serum albumin and of Auoxo6 with serum apoTf invariantly result in gold(III) to gold(I) reduction. Gold(III) reduction, clearly documented by XANES, is accompanied, in both cases, by release of the bipyridyl ligands; for Auoxo6 cleavage of the gold-gold dioxo bridge is also observed. Gold(III) reduction leads to formation of protein-bound gold(I) species, with deeply modified metal coordination environments, as evidenced by EXAFS. In these adducts, the gold(I) centers are probably anchored to the protein through nitrogen donors. In general, these two XAS methods, i.e., XANES and EXAFS, used here jointly, allowed us to gain independent structural information on metallodrug/protein systems; detailed insight into the gold oxidation state and the local environment of protein-bound metal atoms was achieved in the various cases.

  • Details
  • Metrics
Type
research article
DOI
10.1007/s00775-010-0748-5
Web of Science ID

WOS:000288026000012

Author(s)
Messori, L.
Balerna, A.
Ascone, I.
Castellano, C.
Gabbiani, C.
Casini, A.  
Marchioni, C.
Jaouen, G.
Congiu Castellano, A.
Date Issued

2011

Publisher

Springer Verlag

Published in
Journal of Biological Inorganic Chemistry
Volume

16

Issue

3

Start page

491

End page

499

Subjects

X-ray absorption spectroscopy

•

Gold compound

•

Protein

•

Cytotoxicity

•

Platinum(Iv) Anticancer Agents

•

Human Blood-Plasma

•

Gold(Iii) Complexes

•

Binding Properties

•

Solution Chemistry

•

Bipyridyl Ligands

•

Crystal-Structure

•

Cancer-Cells

•

Albumin

•

Metallodrugs

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
LCOM  
Available on Infoscience
December 22, 2010
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/62457
Logo EPFL, École polytechnique fédérale de Lausanne
  • Contact
  • infoscience@epfl.ch

  • Follow us on Facebook
  • Follow us on Instagram
  • Follow us on LinkedIn
  • Follow us on X
  • Follow us on Youtube
AccessibilityLegal noticePrivacy policyCookie settingsEnd User AgreementGet helpFeedback

Infoscience is a service managed and provided by the Library and IT Services of EPFL. © EPFL, tous droits réservés