title: Protein glycation by ADP-ribose: studies of model conjugates.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Texas College of Osteopathic Medicine, University of North Texas, Fort Worth 76107.
authors.forename: D
authors.initials: D
authors.lastname: Cervantes-Laurean
authors.forename: D E
authors.initials: DE
authors.lastname: Minter
authors.forename: E L
authors.initials: EL
authors.lastname: Jacobson
authors.forename: M K
authors.initials: MK
authors.lastname: Jacobson
mesh_terms: 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
chemical_list: D000588:Amines; D006023:Glycoproteins; D007202:Indicators and Reagents; D011506:Proteins; D000246:Adenosine Diphosphate Ribose; D008239:Lysine