Aldehydes or dicarbonyls in non-enzymic glycosylation of proteins

Abstract

The non-enzymic post-translational glycosylation of certain proteins has been implicated in the production of diabetic sequelae. In the present paper the possibility that it is not the glucose aldehyde that binds to proteins but a dicarbonyl autoxidation product is investigated. Earlier experiments may not have distinguished between these two possibilities. The rate of binding of 2-deoxyglucose (a non-autoxidizable sugar) to lens α-crystallin is compared with that of glucose (an autoxidizable sugar). The stabilized Schiff-base adducts from reaction of glucose with glycine were isolated. The structure of the adducts was investigated by using proton n.m.r. and fast-atom-bombardment mass spectroscopy to distinguish whether they are the product of aldehyde or dicarbonyl addition. We conclude that it is the open-chain aldehyde of glucose that binds initially to amino groups and that there is no participation of dicarbonyl autoxidation products in the initial non-enzymic protein glycosylation reaction.