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Bioorg Med Chem Lett. 2011 Jan 1;21(1):255-8. doi: 10.1016/j.bmcl.2010.11.018. Epub 2010 Nov 5.

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

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1
Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Moscow 117871, Russia.

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-d(2)-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 D(2)Lys and its incorporation via normal Lys turnover suggests new approaches to mitigating LOX-associated pathologies.

PMID:
21106372
DOI:
10.1016/j.bmcl.2010.11.018
[Indexed for MEDLINE]
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