This news release is available in Japanese.
A new way to synthesize a molecule implicated in diseases like diabetes is offering researchers a long sought means to study how reactions with glucose can negatively alter the structure of important proteins of the human body. The accumulation of glucosepane on disease-associated proteins hints that it may play a role in a variety of health complications, including diabetes, but the difficulty of isolating glucosepane from the body has impeded research efforts. Synthetically producing glucosepane offers an appealing solution to better study the roles of this compound in human disease. Glucosepane exists in eight different stereoisomers (variations); to identify a method by which to synthesize these, Cristian Draghici and colleagues started with the suspected core structure of glucosepane, based on previous research, and used theoretical computations to identify plausible arrangements of the different stereoisomers. From there, the authors outline a total of eight steps required to produce the core structure of two of the isomers of glucosepane, resulting in a 12% overall yield. They also suggest routes to the remaining six isomers by adjusting the structure of the starting materials. With the synthesis of glucosepane's various forms now possible, a closer analysis of this culprit substance may uncover how exactly it contributes to health complications such as diabetes, and a means to counter its detrimental effects. A Perspective by Dale Boger provides more context.
Article #9: "Concise total synthesis of glucosepane," by C. Draghici; T. Wang; D.A. Spiegel at Yale University in New Haven, CT; C. Draghici at Broad Institute of MIT and Harvard in Cambridge, MA; T. Wang at Harvard University in Cambridge, MA.
Article #3: "When sugar is not so sweet," by D.L. Boger at The Scripps Research Institute in La Jolla, CA.