PROTEIN GLYCATION BY ADP-RIBOSE - STUDIES OF MODEL CONJUGATES
PROTEIN GLYCATION BY ADP-RIBOSE - STUDIES OF MODEL CONJUGATES
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DOI：
10.1021/bi00057a017
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发表时间：
1993-02-16
期刊：
影响因子：
2.9
通讯作者：
JACOBSON, MK
中科院分区：
文献类型：
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作者：
CERVANTESLAUREAN, D;MINTER, DE;JACOBSON, MK
己糖对蛋白质的糖基化参与了许多疾病的病理生理学以及衰老过程。对ADP-核糖聚合物代谢的研究表明，DNA损伤后，细胞核中会快速产生游离的ADP-核糖。ADP-核糖对蛋白质的糖基化作用已有报道，但其化学机制尚不清楚。本文介绍了ADP-核糖对赖氨酸残基进行蛋白质糖基化的模型偶联物的合成和表征。从ADP-核糖和正丁胺中分离并鉴定了两种稳定的偶联物。通过Amadori重排反应，证明这两种化合物都是由席夫碱衍生的酮胺。酮胺的化学稳定性使它们有别于ADP-核糖修饰的所有类型的酶蛋白。此外，它们的化学性质表明，先前报道的致癌物处理细胞中组蛋白H1的修饰是由于ADP-核糖的糖基化。
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 ketoamines 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.