科研之友
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摘要
The (1)H nuclear magnetic resonance spectroscopy was applied to study the reaction of the dipeptide glycyl-D, L-methionine (H-Gly-D,L-Met-OH) and its N-acetylated derivative (Ac-Gly-D, L-Met-OH) with hydrogen tetrachloridoaurate(III) (H[AuCl(4)]). The corresponding peptide and [AuCl(4)](-) were reacted in 1: 1, 2: 1, and 3: 1 molar ratios, and all reactions were performed at pD 2.45 in 0.01 M DCl as solvent and at 25 degrees C. It was found that the first step of these reactions is coordination of Au(III) to the thioether sulfur atom with formation of the gold(III)-peptide complex [AuCl(3)(R-Gly-Met-OH-S)] (R=H or Ac). This intermediate gold(III) complex further reacts with an additional methionine residue to generate the R-Gly-Met-OH chlorosulfonium cation as the second intermediate product, which readily undergoes hydrolysis to give the corresponding sulfoxide. The oxidation of the methionine residue in the reaction between H-Gly-D, L-Met-OH and [AuCl(4)](-) was five times faster (k(2)=0.363 +/- 0.074 M(-1)s(-1)) in comparison to the same process with N-acetylated derivative of this peptide (k(2)=0.074 +/- 0.007 M(-1)s(-1)). The difference in the oxidation rates between these two peptides can be attributed to the free terminal amino group of H-Gly-D, L-Met-OH dipeptide. The mechanism of this redox process is discussed and, for its clarification, the reaction of the H-Gly-D, L-Met-OH dipeptide with [AuCl(4)](-) was additionally investigated by UV-Vis and cyclic voltammetry techniques. From these measurements, it was shown that the [AuCl(2)](-) complex under these experimental conditions has a strong tendency to disproportionate, forming [AuCl(4)](-) and metallic gold. This study contributes to a better understanding of the mechanism of the Au(III)-induced oxidation of methionine and methionine-containing peptides in relation to the severe toxicity of anti-arthritic and anticancer gold-based drugs.
- 出版日期2011
