albumin - publications

Predict more albumin - ligand interactions now!


1. Dalton Trans. 2012 Apr 5. [Epub ahead of print]

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

Correia I, Jakusch T, Cobbinna E, Mehtab S, Tomaz I, Nagy NV, Rockenbauer A,
Costa Pessoa J, Kiss T.

Centro de Química Estrutural, Instituto Superior Técnico, Av. Rovisco Pais 1,
1049-001 Lisbon, Portugal. joao.pessoa@ist.utl.pt.

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(IV)O 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(IV)O-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(IV)O to bind
albumin. The possibility and importance of ternary complex formation between
V(IV)O, 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(IV)OL(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(IV)OL(2) +
HSA ⇆ V(IV)OL(2)(HSA) is hpno > pic ≥ mal > dhp. (V(IV)OL)(n)(HSA) type complexes
are detected exclusively with pic. Based on the spectroscopic studies we propose
that in the (V(IV)OL(2))(n)(HSA) species the protein bounds to vanadium through
the histidine side chains.

PMID: 22476413 [PubMed - as supplied by publisher]