Site-Specific Binding of Quinones to Proteins through Thiol Addition and Addition−Elimination Reactions

• Published in: Journal of the American Chemical Society 2005-05, Vol.127 (17), p.6140-6141
• Main Authors: Li, Wen-Wu, Heinze, Jürgen, Haehnel, Wolfgang
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Benzoquinones - chemistry; Benzoquinones - metabolism; Biological and medical sciences; Cytochromes c - chemistry; Cytochromes c - metabolism; Electrochemistry; Fundamental and applied biological sciences. Psychology; Mechanisms. Catalysis. Electron transfer. Models; Models, Molecular; Molecular biophysics; Molecular Sequence Data; Peptide Fragments - chemistry; Peptide Fragments - metabolism; Physical chemistry in biology; Protein Binding; Protein Conformation; Quinones - chemistry; Quinones - metabolism; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Structure-Activity Relationship; Substrate Specificity; Sulfhydryl Compounds - chemistry; Sulfhydryl Compounds - metabolism; Vitamin K 3 - chemistry; Vitamin K 3 - metabolism
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja050974x

Ubiquinone-0, menaquinone-0, and 2,3,5-trimethyl-1,4-benzoquinone were site-specifically bound to free cysteine of proteins (yeast iso-1 cytochrome c as a model protein) through thioether bond formation. Model thioether quinone conjugates showed unexpected reactivity to cysteine of proteins as their parent quinones by thiol addition−elimination reaction. Cyclic voltammetry studies of the model compounds showed only minor differences in their redox potentials as compared to their parent quinones. Thioether ligation provides a general, simple, and fast method to construct model quinone protein systems. In addition, these studies also contribute to the understanding of biological activities, toxicity, and anti-cancer mechanism of quinones and thioether quinone adducts.