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Summary
Inadvertent modifications of proteins by metabolites have been implicated in numerous disorders, including inflammation, diabetes, and human aging. Despite their importance, little is known about the formation and effect of such protein modifications. A major obstacle to the study of their role in disease is the limited access to pure samples of protein modifications of this kind. On page 294 of this issue, Draghici et al. (1) provide a much-needed advance by reporting the total synthesis of glucosepane (1, see the first figure), the core of a harmful protein modification that arises from reaction of the common metabolite glucose (4, see the second figure).