Glycation is the result of covalent bonding of a free amino group of biological macromolecules with a reducing sugar, which results in the formation of a Schiff base that undergoes rearrangement, dehydration and cyclization to form a more stable Amadori product. The final products of nonenzymatic glycation of biomacromolecules like DNA, proteins and lipids are known as advanced glycation end products (AGEs). AGEs may be generated rapidly or over long times stimulated by distinct triggering mechanisms, thereby accounting for their roles in multiple settings and disease states. Both Schiff base and Amadori glycation products generate free radicals resulting in decline of antioxidant defense mechanisms and can damage cellular organelles and enzymes. This critical review primarily focuses on the mechanistic insight of glycation and the most probable route for the formation of glycation products and their therapeutic interventions. Furthermore, the prevention of glycation reaction using therapeutic drugs such as metformin, pyridoxamine and aminoguanidine (AG) are discussed with special emphasis on the novel concept of the bioconjugation of these drugs like, AG with gold nanoparticles (GNPs). At or above 10 mM concentration, AG is found to be toxic and therefore has serious health concerns, and the study warrants doing this novel bioconjugation of AG with GNPs. This approach might increase the efficacy of the AG at a reduced concentration with low or no toxicity. Using the concept of synthesis of GNPs with abovementioned drugs, it is assumed that toxicity of various drugs which are used at high doses can be minimized more effectively.

Proteins undergo glycation resulting in the generation of advanced glycation end products (AGEs) that play a central role in the onset and advancement of diabetes‐associated secondary complications. Aminoguanidine (AG) acts as an antiglycating agent by inhibiting AGE generation by blocking reactive carbonyl species (RCS) like, methylglyoxal (MGO). Previous studies on antiglycating behavior of AG gave promising results in the treatment of diabetes‐associated microvascular complications, but it was discontinued as it was found to be toxic at high concentrations (>10 mmol/L). The current article aims at glycation inhibition by conjugating gold nanoparticles (Gnp) with less concentration of AG (0.5‐1.0 mmol/L). The HPLC results showed that AG‐Gnp fairly hampers the formation of glycation adducts. Moreover, the in vivo studies revealed AG‐Gnp mediated inhibition in the production of total‐AGEs and ‐N^ε‐(carboxymethyl)lysine (CML) in the diabetic rat model. This inhibition was found to be directly correlated with the antioxidant parameters, blood glucose, insulin, and glycosylated hemoglobin levels. Furthermore, the histopathology of AG‐Gnp‐treated rats showed good recovery in the damaged pancreatic tissue as compared to diabetic rats. We propose that this approach might increase the efficacy of AG at relatively low concentrations to avoid toxicity and might facilitate to overcome the hazardous actions of antiglycating drugs.

Non-enzymatic glycation of DNA both in vivo and in vitro results in generation of free radicals, known as glycoxidation. Glycoxidation leads to structural perturbation of DNA resulting in generation of neo-antigenic epitopes having implication in autoimmune disorders like diabetes mellitus. In this study human placental DNA was glycated with methylglyoxal (MG) and lysine (Lys) in the presence of Cu²⁺ and its auto-antibody binding was probed in Type 1 diabetes patients. Glycation was carried out by incubating DNA with MG, Lys and Cu²⁺ for 24 h at 37 °C. Carboxyethyl deoxyguanosine (CEdG) formed in glycation reaction was studied by LC-MS and the pathway for Amadori formation was studied by ESI-MS techniques. Furthermore, binding characteristics of auto-antibodies in diabetes patients were assessed by direct binding, competitive ELISA and band shift assay. DNA glycation with MG, Lys and Cu²⁺ results in the formation of CEdG (marker of DNA glycation) which was confirmed by LC-MS. The intermediate stages of glycation were confirmed by ESI-MS technique. Serum from diabetes patients exhibited enhanced binding and specificity for glycated DNA as compared to native form. Glycation of DNA has resulted in structural perturbation causing generation of neo-antigenic epitopes thus recognizing auto-antibodies in diabetes.