Antimony(V) complex formation with adenine nuelcosides in aqueous solution

被引:52
作者
Demicheli, C
Frézard, F
Lecouvey, M
Garnier-Suillerot, A
机构
[1] Univ Fed Minas Gerais, Inst Ciencias Exatas, Dept Quim, BR-31270901 Belo Horizonte, MG, Brazil
[2] Univ Paris 13, UMR CNRS 7033, Lab Physicochim Biomol & Cellulaire, F-93017 Bobigny, France
[3] Univ Paris 13, UMR CNRS 7031, Lab Chim Struct & Spect Biomol, F-93017 Bobigny, France
[4] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Fisiol & Biofis, BR-31270901 Belo Horizonte, MG, Brazil
来源
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS | 2002年 / 1570卷 / 03期
关键词
nucleoside; adenosine; antimony; meglumine antimonate; mechanism of action; leishmaniasis;
D O I
10.1016/S0304-4165(02)00198-8
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Despite the clinical use of pentavalent antimonial drugs for over half a century, their mode of action against leishmaniasis remains poorly understood. In this paper, we investigated the ability of Sb(V) to form in aqueous solution complexes with adenine nucleosides and deoxynucleosides, using circular dichroism (CD) and 1 H and 13 C NMR spectroscopies. We report that the ribonucleosides, adenosine (A) and adenosine monophosphate (AMP), form in water complexes with Sb(V), as evidenced by the changes induced in their CD spectra. On the other hand, 2'-deoxyadenosine (dA) did not show such a change. CD titration of the ribonucleosides with Sb(V) suggests the formation of 1:2 Sb(V)-nucleoside complexes. NMR analysis indicates that Sb(V) binds to the sugar moiety at the 2' position. Furthermore, the incubation of the antimonial drug, meglumine antimonate, with adenosine at 37 degreesC led to the transfer of Sb(V) from its original ligand to the nucleoside molecule, at acidic pH (pH 5), but not at neutral pH (7.2). Our data therefore suggests that the formation of such complexes may take place in vivo within the acidic cell compartments, including the phagolysosome of macrophage in which Leishmania resides. (C) 2002 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:192 / 198
页数:7
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