Shigeta Tomoaki, Sasamoto Kazumi, Yamamoto Tetsuro
Bloom Technology Corporation, 3-14-3 Minamikumamoto, Kumamoto, 860-0812, Japan.
Biochem Biophys Rep. 2021 Mar 9;26:100963. doi: 10.1016/j.bbrep.2021.100963. eCollection 2021 Jul.
Reducing sugars and reactive aldehydes, such as glyceraldehyde, non-enzymatically react with amino or guanidino groups of proteins to form advanced glycation end-products (AGEs) by the Maillard reaction that involves Schiff base formation followed by Amadori rearrangement. AGEs are found relatively in abundance in the human eye and to accumulate at a higher rate in diseases that impair vision such as cataract, diabetic retinopathy or age-related macular degeneration. We identified two novel AGEs of pyrrolopyridinium lysine dimer derived from glyceraldehyde, PPG1 and PPG2, in the Maillard reaction of -acetyl-l-lysine with glyceraldehyde under physiological conditions. Having fluorophores similar to that of vesperlysine A, which was isolated from the human lens, PPGs were found to act as photosensitizers producing singlet oxygen in response to blue light irradiation. Moreover, PPG2 interacts with receptor for AGE (RAGE) with a higher binding affinity than GLAP, a well-known ligand of the receptor. We also proposed a pathway to form PPGs and discussed how they would be formed . As glyceraldehyde-derived AGEs have been studied extensively in connection with various hyperglycemia-related diseases, further studies will be required to find PPGs such as in the lens or other tissues.
还原糖和活性醛类，如甘油醛，会与蛋白质的氨基或胍基发生非酶反应，通过美拉德反应形成晚期糖基化终产物（AGEs），该反应涉及席夫碱的形成，随后是阿玛多里重排。AGEs在人眼中相对丰富，并在损害视力的疾病（如白内障、糖尿病视网膜病变或年龄相关性黄斑变性）中以更高的速率积累。我们在生理条件下，通过α-乙酰-L-赖氨酸与甘油醛的美拉德反应，鉴定出了两种源自甘油醛的新型吡咯并吡啶赖氨酸二聚体AGEs，即PPG1和PPG2。由于PPGs具有与从人晶状体中分离出的vesperlysine A类似的荧光团，它们被发现可作为光敏剂，在蓝光照射下产生单线态氧。此外，PPG2与晚期糖基化终产物受体（RAGE）相互作用，其结合亲和力高于该受体的知名配体GLAP。我们还提出了形成PPGs的途径，并讨论了它们将如何形成。由于与各种高血糖相关疾病相关的源自甘油醛的AGEs已得到广泛研究，因此需要进一步研究以在晶状体或其他组织中找到PPGs。
