PMID: 11911173Mar 26, 2002Paper

DYN 12, a small molecule inhibitor of the enzyme amadorase, lowers plasma 3-deoxyglucosone levels in diabetic rats

Diabetes Technology & Therapeutics
F KapplerT Brown

Abstract

3-Deoxyglucosone (3DG) is a highly reactive alpha-dicarbonyl sugar and potent protein cross-linker that is important in the formation of advanced glycation end products (AGEs), which have been postulated to lead to the development of diabetic complications. (1) Reducing 3DG levels in diabetics is a potentially effective therapy to slow the development of diabetic complications. Standard biochemical methods were used to isolate, identify, and characterize the enzyme responsible for the production of 3DG, in order to develop an effective therapeutic agent against this target. We have purified and characterized Amadorase, a fructosamine-3-kinase, and demonstrated both in vitro and in vivo that it is responsible for the production of 3-deoxyglucosone (3DG). A small molecule inhibitor of Amadorase, DYN 12, significantly lowered plasma levels of 3DG in diabetic (by 46%, p = 0.0116) and normal (by 43%, p = 0.0024) rats. These data are the first indications that it is possible to significantly reduce 3DG production in diabetics and thus possibly reduce the development of diabetic complications.

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Citations

Feb 25, 2011·Applied Microbiology and Biotechnology·Veronika Maria DeppeFriedhelm Meinhardt
Mar 15, 2011·Applied and Environmental Microbiology·Veronika Maria DeppeFriedhelm Meinhardt
Sep 23, 2009·Wound Repair and Regeneration : Official Publication of the Wound Healing Society [and] the European Tissue Repair Society·Danielle T Loughlin, Carol M Artlett
Oct 22, 2003·Archives of Biochemistry and Biophysics·Xinle Wu, Vincent M Monnier
Jan 30, 2015·Journal of Diabetes Science and Technology·Miho KameyaKoji Sode

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