AGING OF PROTEINS - ISOLATION AND IDENTIFICATION OF A FLUORESCENT CHROMOPHORE FROM THE REACTION OF POLYPEPTIDES WITH GLUCOSE
AGING OF PROTEINS - ISOLATION AND IDENTIFICATION OF A FLUORESCENT CHROMOPHORE FROM THE REACTION OF POLYPEPTIDES WITH GLUCOSE
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DOI：
10.1073/pnas.81.9.2684
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发表时间：
1984-01-01
期刊：
影响因子：
--
通讯作者：
CERAMI, A
中科院分区：
文献类型：
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作者：
PONGOR, S;ULRICH, PC;CERAMI, A
已知长时间暴露于葡萄糖的蛋白质会发生物理化学变化，包括交联和形成表征结构不佳的棕色荧光色素。棕色的聚（L-赖氨酸）和棕色的牛血清白蛋白的酸水解释放出一个主要的荧光发色团，碱化后可提取到有机溶剂中，并可通过硅胶色谱法纯化。该化合物的荧光性质非常类似于大量棕色多肽的荧光性质。通过NMR、质谱和化学衍生化，该化合物的结构被指定为2-（2-呋喃甲酰基）-4（5）-（2-呋喃基）-1H-咪唑（FFI）。通过呋喃乙二醛和氨的独立化学合成得到确认。在FFI中掺入2个肽衍生的胺N和2个葡萄糖残基强烈表明肽结合的FFI前体与体内葡萄糖对蛋白质的交联有关。这种反应对理解葡萄糖介导的蛋白质修饰及其在糖尿病和衰老并发症中的作用具有潜在意义。
Proteins exposed to glucose over long periods are known to undergo physicochemical changes including crosslinking and formation of brown fluorescent pigments of poorly characterized structure. Acid hydrolysis of both browned poly(L-lysine) and browned bovine serum albumin releases a major fluorescent chromophore, which after alkalinization is extractable into organic solvents and which can be purified by silica gel chromatography. The fluorescence properties of this compound very closely resemble those of the bulk browned polypeptides. By NMR, mass spectroscopy and chemical derivatization, this compound is assigned the structure 2-(2-furoyl)-4(5)-(2-furanyl)-1H-imidazole (FFI). Confirmation was obtained by independent chemical synthesis from furylglyoxal and ammonia. The incorporation of 2 peptide-derived amine N and 2 glucose residues in FFI strongly suggests that peptide-bound FFI precursors are implicated in the crosslinking of proteins by glucose in vivo. This reaction has potential implications in the understanding of glucose-mediated protein modifications and their role in the complications of diabetes and aging.