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A new inhibitor for fructosamine 3‐kinase (Amadorase)
Author(s) -
Tsai Henry J.,
Chou ShanYen,
Kappler Frank,
Schwartz Michael L.,
Tobia Annette M.
Publication year - 2006
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.20105
Subject(s) - glycation , fructosamine , chemistry , biochemistry , enzyme , maillard reaction , substrate (aquarium) , diabetes mellitus , medicine , endocrinology , biology , receptor , ecology
Non‐enzymatic glycation is a Maillard reaction that occurs spontaneously between glucose and proteins and results in the accumulation of advanced glycation end products (AGEs), which are believed to be one of the causes for age‐related tissue damage. Fructosamine 3‐kinase (FN3K) is an enzyme involved in the protein deglycation process by fructosyl phosphorylation, returning amino acid residues to their pristine state with 3‐deoxyglucosone (3‐DG) and inorganic phosphate as by‐products. 3‐DG is a very reactive electrophile that is even more potent at generating AGEs than glucose; therefore, inhibitors specific to FN3K have been suggested as a means to suppress 3‐DG formation. Dyn‐12 is a substrate mimicking inhibitor with an IC 50 value of approximately 6 mM. We report a new hydrophobic competitive inhibitor with respect to fructolysine that has an IC 50 of 1.7 mM. Drug Dev. Res. 67:448–455, 2006. © 2006 Wiley‐Liss, Inc.