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

NB Pestov, IA Okkelman, VV Shmanai…

Index: Pestov, Nikolay B.; Okkelman, Irina A.; Shmanai, Vadim V.; Hurski, Alaksiej L.; Giaccia, Amato J.; Shchepinov, Mikhail S. Bioorganic and Medicinal Chemistry Letters, 2011 , vol. 21, # 1 p. 255 - 258

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Citation Number: 5

Abstract

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 ...