Protein glycation by ADP-ribose: studies of model conjugates.
Protein glycation by hexoses has been implicated in the pathophysiology of a number of diseases as well as the aging process. Studies of ADP-ribose polymer metabolism have shown that free ADP-ribose is generated at high rates in the cell nucleus following DNA damage. Protein glycation by ADP-ribose has been reported although the chemistry is not understood. Described here is the synthesis and characterization of model conjugates for protein glycation of lysine residues by ADP-ribose. Two stable conjugates derived from ADP-ribose and n-butylamine were isolated and characterized. Both conjugates were shown to be ketoamines derived from a Schiff base by an Amadori rearrangement. The chemical stability of the ketamines allowed them to be differentiated from all classes of enzymic protein modification by ADP-ribose. Further, their chemical properties suggest that a previous report of histone H1 modification in carcinogen treated cells was due to glycation by ADP-ribose.
Cervantes-Laurean
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Department of Biochemistry and Molecular Biology, Texas College of Osteopathic Medicine, University of North Texas, Fort Worth 76107.
Minter
D E
DE
Jacobson
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EL
Jacobson
M K
MK
D000246:Adenosine Diphosphate Ribose / Q000737:chemistry* / Q000378:metabolism*; D000588:Amines; D003124:Colorimetry; D006023:Glycoproteins / Q000378:metabolism*; D006031:Glycosylation; D007202:Indicators and Reagents; D007700:Kinetics; D008239:Lysine; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D011506:Proteins / Q000378:metabolism; D013997:Time Factors
D000588:Amines; D006023:Glycoproteins; D007202:Indicators and Reagents; D011506:Proteins; D000246:Adenosine Diphosphate Ribose; D008239:Lysine