Open AccessInteraction of antimony tartrate with the tripeptide glutathione
Author(s) -
Sun Hongzhe,
Yan Siu Cheong,
Cheng Wing Shan
Publication year - 2000
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1046/j.1432-1327.2000.01605.x
Subject(s) - chemistry , tripeptide , glutathione , tartrate , antimony , electrospray ionization , deprotonation , nuclear magnetic resonance spectroscopy , cysteine , aqueous solution , nuclear chemistry , inorganic chemistry , stereochemistry , mass spectrometry , organic chemistry , peptide , chromatography , biochemistry , ion , enzyme
The tripeptide glutathione (γ‐ l ‐Glu‐ l ‐Cys‐Gly, GSH) is thought to play an important role in the biological processing of antimony drugs. We have studied the complexation of the antileishmanial drug potassium antimony(III) tartrate to GSH in both aqueous solution and intact red blood cells by NMR spectroscopy and electrospray ionization mass spectrometry. The deprotonated thiol group of the cysteine residue is shown to be the only binding site for Sb(III), and a complex with the stoichiometry [Sb(GS) 3 ] is formed. The stability constant for [Sb(GS) 3 ] was determined to be log K 25 ( I = 0.1 m , 298 K) based on a competition reaction between tartrate and GSH at different pH* values. In spite of being highly thermodynamically stable, the complex is kinetically labile. The rate of exchange of GSH between its free and Sb‐bound form is pH‐dependent, ranging from slow exchange on the 1 H‐NMR timescale at low pH (2 s −1 at pH 3.2) to relatively rapid exchange at biological pH (> 440 s −1 ). Such facile exchange may be important in the transport of Sb(III) in various biofluids and tissues in vivo . Our spin–echo 1 H‐NMR data show that Sb(III) rapidly entered red blood cell walls and was complexed by intracellular glutathione.