NDA@SZTAKI

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

Enyedy, Éva Anna

Farkas, Etelka

DĂśmĂśtĂśr, Orsolya

Santos, M. A.

Elsevier

2011

QD01 Analytical chemistry / analitikai kĂŠmia

QD03 Inorganic chemistry / szervetlen kĂŠmia

QH3011 Biochemistry / biokĂŠmia

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 ΟM), 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. Š 2010 Elsevier Inc. All rights reserved.

angol

Article

PeerReviewed

info:eu-repo/semantics/article

text

http://real.mtak.hu/36642/1/real_JIB_2011_105_444.pdf

Enyedy, Éva Anna and Farkas, Etelka and Dömötör, Orsolya and Santos, M. A. (2011) Interaction of folic acid and some matrix metalloproteinase (MMP) inhibitor folate-γ-hydroxamate derivatives with Zn(II) and human serum albumin. JOURNAL OF INORGANIC BIOCHEMISTRY, 105 (3). pp. 444-453. ISSN 0162-0134

http://real.mtak.hu/36642/

http://dx.doi.org/10.1016/j.jinorgbio.2010.12.008

MTMT:1505568; doi:10.1016/j.jinorgbio.2010.12.008