Interaction of folic acid and some matrix metalloproteinase (MMP) inhibitor folate-γ-hydroxamate derivatives with Zn(II) and human serum albumin

E. Enyedy, E. Farkas, Orsolya Dömötör, M. Amélia Santos

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Human serum albumin binding of folic acid and its γ-hydroxamate/ carboxylate derivatives was studied by ultrafiltration and spectrofluorimetry, and it was found that the ligands exhibit a moderate binding (KD ∼ 2-50 μM), and the folate-γ-phenylalanine represents the highest conditional binding constant towards albumin. This feature may have importance in the serum transport processes of these ligands. Interaction of folic acid and its derivatives with Zn(II) was investigated in aqueous solution to obtain the composition and stabilities of the complexes by the means of pH-potentiometry, 1H NMR and electrospray ionization mass spectrometry, together with the characterization of the proton dissociation processes and the hydro-lipophilic properties of the ligands. The formation of mono-ligand complexes was demonstrated in all cases and the contribution of the glutamyl carboxylates to the coordination was excluded. Binding of folic acid and its γ-carboxylate derivatives to Zn(II) via the pteridine moiety is suggested, while the (O,O) coordination fashion of the folate-γ-hydroxamate ligands has importance in their inhibitory activity against Zn(II)-containing matrix metalloproteinases. It was found that the enzyme inhibition of these folate-γ-hydroxamate ligands is mainly tuned by other features, such as the lipophilic character rather than the Zn(II)-chelate stability.

Original languageEnglish
Pages (from-to)444-453
Number of pages10
JournalJournal of Inorganic Biochemistry
Volume105
Issue number3
DOIs
Publication statusPublished - Mar 2011

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Matrix Metalloproteinase Inhibitors
Folic Acid
Serum Albumin
Ligands
Derivatives
Potentiometry
Pteridines
Enzyme inhibition
Electrospray ionization
Electrospray Ionization Mass Spectrometry
Ultrafiltration
Matrix Metalloproteinases
Phenylalanine
Mass spectrometry
Protons
Albumins
Nuclear magnetic resonance
Enzymes
Serum
Chemical analysis

Keywords

  • Folate-hydroxamate conjugates
  • Folic acid
  • Protein-ligand interaction
  • Solution equilibrium
  • Stability constants
  • Ultrafiltration

ASJC Scopus subject areas

  • Biochemistry
  • Inorganic Chemistry

Cite this

Interaction of folic acid and some matrix metalloproteinase (MMP) inhibitor folate-γ-hydroxamate derivatives with Zn(II) and human serum albumin. / Enyedy, E.; Farkas, E.; Dömötör, Orsolya; Santos, M. Amélia.

In: Journal of Inorganic Biochemistry, Vol. 105, No. 3, 03.2011, p. 444-453.

Research output: Contribution to journalArticle

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