Glycoxidation of biological macromolecules: A critical approach to halt the menace of glycation

Abstract

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.

An Immunohistochemical Analysis to Validate the Rationale behind the Enhanced Immunogenicity of D-Ribosylated Low Density Lipo-Protein

“…There are also couple of recent reports for the presence of the auto-antibodies in the sera of the cancer patients which needs to be validated further [37]. Therefore the need of the hour is to stop this dreaded reaction using novel approach like nanoconjugation [38], [39]. Our research group has recently shown some medicinal plants that have potent antioxidant property like Phyllanthus virgatus , Ficus virens and Boerhaavia diffusa [40]–[42].…”

Long-Term Stability of Glucose Responsive Dextran Methacrylate-Concanavalin A Methacrylamide Gels as Part of an Implantable Artificial Pancreas

“…It is also unknown if the presence of glucose may increase hydrolytic damage. Certainly proteins in general can be harmed by nonenzymatic glycosylation [16]. In the glucose-free gel, glycosylation would not occur but also the interactive subunits are sterically protected by the insertion of the dextran.…”

Glycation vs. glycosylation: a tale of two different chemistries and biology in Alzheimer’s disease

“…Baynes's group proposed that oxidative stress and damage to proteins in diabetes are due to free radicals from the autoxidation of sugars and sugar adducts to protein and as well as of unsaturated lipids in plasma and membrane proteins [48]. This glycation reaction has been highly implicated in redox balance and therefore this type of reaction is designated as a Bglycoxidation reaction^ [48,49]. Our group previously reported that glycation induces apoptosis by provoking oxidative stress in pancreatic beta cells [50,51], therefore, a similar oxidative stress would be expected in other pathological situations such as neurodegenerative diseases.…”