A spectroscopic and electrochemical investigation of the oxidation pathway of glycyl-d,l-methionine and its N-acetyl derivative induced by gold(III)

Abstract

The 1 H nuclear magnetic resonance spectroscopy was applied to study the reaction of the dipeptide glycyl-D,

Oxidation of methionine residue in Gly-Met dipeptide induced by [Au(en)Cl2]+ and influence of the chelated ligand on the rate of this redox process

“…Moreover, the structure of the corresponding sulfoxide as the final product of gold(III)-induced oxidation of methioninecontaining peptides was confirmed by X-ray crystallography [32]. In a continuation of our previous investigations [31,32] H NMR spectra were recorded on a Varian Gemini 2000 spectrometer (200 MHz) using 5-mm NMR tubes. Sodium trimethylsilylpropane-3-sulfonate (TSP, δ 0.00 ppm) was used as an internal reference.…”

“…1). The singlet at 2.71 ppm was assigned to the -S CH 3 H NMR spectroscopy and X-ray crystallography [31,32].…”

“…Gly-Met dipeptide and its N-acetyl derivative, Ac-Gly-Met, proceed in two steps [31]. The first step is a very fast coordination of Au(III) ion to the thioether sulfur with formation of an intermediate gold(III)-peptide complex, [AuCl 3 (R-Gly-Met-S)] (R = H and Ac).…”

“…Moreover, the formed gold(III) complexes with L-histidine-containing peptides are very stable under physiologically relevant conditions with promising cytotoxic properties toward different human tumor cell lines [21]. On the other hand, the reactions of Au(III) with sulfurcontaining amino acids and peptides primarily proceed through the reduction of Au(III) ion and oxidation of sulfur side chain [22][23][24][25][26][27][28][29][30][31][32]. Thus, Au(III) rapidly oxidizes the thiolcontaining amino acid L-cysteine to its disulfide cystine and, afterwards, cleaves the disulfide bond of cystine to give cysteic acid, thereby being reduced to Au(I) and Au(0) [22][23][24][25][26].…”

“…Thus, Au(III) rapidly oxidizes the thiolcontaining amino acid L-cysteine to its disulfide cystine and, afterwards, cleaves the disulfide bond of cystine to give cysteic acid, thereby being reduced to Au(I) and Au(0) [22][23][24][25][26]. Furthermore, Au(III) is capable to oxidize methionine and methionine-containing peptides to the corresponding sulfoxides [27][28][29][30][31][32]. These interactions are thought to be responsible for the toxic side effects of gold-based drugs.…”