Evaluation of the binding of oxovanadium(iv) to human serum albumin

Isabel Correia, T. Jakusch, Enoch Cobbinna, Sameena Mehtab, Isabel Tomaz, N. Nagy, A. Rockenbauer, João Costa Pessoa, T. Kiss

Research output: Contribution to journalArticle

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Abstract

The understanding of the biotransformations of insulin mimetic vanadium complexes in human blood and its transport to target cells is an essential issue in the development of more effective drugs. We present the study of the interaction of oxovanadium(iv) with human serum albumin (HSA) by electron paramagnetic resonance (EPR), circular dichroism (CD) and visible absorption spectroscopy. Metal competition studies were done using Cu II and Zn II as metal probes. The results show that V IVO occupies two types of binding sites in albumin, which compete not only with each other, but also with hydrolysis of the metal ion. In one of the sites the resulting V IVO-HSA complex has a weak visible CD signal and its X-band EPR spectrum may be easily measured. This was assigned to amino acid side chains of the ATCUN site. The other binding site shows stronger signals in the CD in the visible range, but has a hardly measurable EPR signal; it is assigned to the multi metal binding site (MBS) of HSA. Studies with fatted and defatted albumin show the complexity of the system since conformational changes, induced by the binding of fatty acids, decrease the ability of V IVO to bind albumin. The possibility and importance of ternary complex formation between V IVO, HSA and several drug candidates - maltol (mal), picolinic acid (pic), 2-hydroxypyridine-N-oxide (hpno) and 1,2-dimethyl-3-hydroxy-4(1H)- pyridinone (dhp) was also evaluated. In the presence of maltol the CD and EPR spectra significantly change, indicating the formation of ternary VO-HSA-maltol complexes. Modeling studies with amino acids and peptides were used to propose binding modes. Based on quantitative RT EPR measurements and CD data, it was concluded that in the systems with mal, pic, hpno, and dhp (V IVOL 2) n(HSA) species form, where the maximum value for n is at least 6 (mal, pic). The degree of formation of the ternary species, corresponding to the reaction V IVOL 2 + HSA V IVOL 2(HSA) is hpno > pic ≥ mal > dhp. (V IVOL) n(HSA) type complexes are detected exclusively with pic. Based on the spectroscopic studies we propose that in the (V IVOL 2) n(HSA) species the protein bounds to vanadium through the histidine side chains.

Original languageEnglish
Pages (from-to)6477-6487
Number of pages11
JournalDalton Transactions
Volume41
Issue number21
DOIs
Publication statusPublished - Jun 7 2012

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Serum Albumin
Paramagnetic resonance
Albumins
Vanadium
Metals
Binding Sites
Amino Acids
Absorption spectroscopy
Histidine
Pharmaceutical Preparations
Metal ions
maltol
Hydrolysis
Blood
Fatty Acids
picolinic acid
Insulin
Peptides

ASJC Scopus subject areas

  • Inorganic Chemistry

Cite this

Evaluation of the binding of oxovanadium(iv) to human serum albumin. / Correia, Isabel; Jakusch, T.; Cobbinna, Enoch; Mehtab, Sameena; Tomaz, Isabel; Nagy, N.; Rockenbauer, A.; Costa Pessoa, João; Kiss, T.

In: Dalton Transactions, Vol. 41, No. 21, 07.06.2012, p. 6477-6487.

Research output: Contribution to journalArticle

Correia, Isabel ; Jakusch, T. ; Cobbinna, Enoch ; Mehtab, Sameena ; Tomaz, Isabel ; Nagy, N. ; Rockenbauer, A. ; Costa Pessoa, João ; Kiss, T. / Evaluation of the binding of oxovanadium(iv) to human serum albumin. In: Dalton Transactions. 2012 ; Vol. 41, No. 21. pp. 6477-6487.
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