Control of lysyl oxidase activity through site-specific deuteration of lysine

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• 作者：Nikolay B. Pestov ; Irina A. Okkelman ; Vadim V. Shmanai ; Alaksiej L. Hurski ; Amato J. Giaccia ; Mikhail S. Shchepinov
• 关键词：Lysyl oxidase ; Isotope effect
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2011
• 出版时间：1 January 2011
• 年：2011
• 卷：21
• 期：1
• 页码：255-258
• 全文大小：332 K

文摘

Lysyl oxidase (LOX) is implicated in several extracellular matrix related disorders, including fibrosis and cancer. Methods of inhibition of LOX in vivo include antibodies, copper sequestration and toxic small molecules such as β-aminopropionitrile. Here, we propose a novel approach to modulation of LOX activity based on the kinetic isotope effect (KIE). We show that 6,6-d₂-lysine is oxidised by LOX at substantially lower rate, with apparent deuterium effect on V_max/K_m as high as 4.35 ± 0.22. Lys is an essential nutrient, so dietary ingestion of D₂Lys and its incorporation via normal Lys turnover suggests new approaches to mitigating LOX-associated pathologies.