Glucosepane, a non-enzymatic protein crosslink, is formed from the slow reaction of glucose with the nucleophilic residues lysine and arginine, resulting in protein damage. This product has been observed in human tissue samples, with significantly more glucosepane formed in diabetics and the elderly. Moreover, increased glucosepane levels have been strongly correlated with various diabetic complications, including diabetic neuropathy, nephropathy, and retinopathy. This correlative evidence has led researchers to speculate about the potential mechanistic underpinnings of glucosepane in disease. However, concrete experimentation to test these hypotheses has been notably absent.<br/><br/>In an effort to facilitate further studies on glucosepane, our lab has leveraged our synthetic capabilities towards a bottom-up approach, where we aim to gain access to synthetic glucosepane constructs that can then be used to test long-held hypotheses in the field. Having recently published the first total synthesis of glucosepane, we are working to incorporate the molecule into more physiologically relevant systems and developing tools, such as antibodies, to better probe glucosepane’s effects on human health and biology.

From synthesis to pathology: Identifying glucosepane’s role in diabetes and aging

253rd National Meeting (2017)

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