Research Projects

Amyloid aggregation is an extreme trait noticed in age-related diseases, e.g., Alzheimer's (AD) and Type 2 diabetes (T2D) related with self-assembly and misfolding of various proteins. Inhibition of amyloid aggregation is regarded as one of the most challenging, and highlighted for the treatment of various incurable and deadly metabolic and neurodegenerative diseases. Throughout the amyloid aggregation process, insoluble amyloid protofibrils are formed as toxic intermediate oligomer species. Moreover, the current treatment strategy is mainly focused on the prevention of the production of toxic oligomer species and slowing down the secondary nucleation process of amyloid aggregation. Cellular oxidative stress is one of the crucial factors for triggering protein misfolding and other neurodegenerative or metabolic diseases. Thus, searching for novel compounds that can inhibit or delay amyloid aggregation and related toxicity is a beneficial way to develop new therapeutic approaches. Apart from several types of inhibitors, polymeric materials are the potential to inhibit amyloid aggregation as they have flexible molecular weight, various architecture and functionality, high biocompatibility and bioavailability. Antioxidants have an effective role in the prevention of protein misfolding and other metabolic or neurodegenerative disorders. But these molecules are feebly water soluble that sluggish their bioavailability and are oxidised under aerobic or enzymatic conditions. Hence, to overcome such annoying problems we will pick antioxidant conjugated water-soluble polymers which will act as mechanism-based inhibitors of amyloid aggregations. Interesting biological activities and amyloid aggregation inhibitory potency of naturally occurring vanillin, makes it cherished antioxidant-based inhibitor for the amyloid related diseases. We hypothesize that vanillin may be considered as good for Aβ and hIAPP amyloid aggregations. To enhance the water solubility and biocompatibility of the inhibitor we will design and synthesise of vanillin-based glycopolymer with pendant sugar. In this proposal our primary research objectives are; (i) design and synthesis of vanillin conjugated glycopolymers with pendant sugar moieties as amyloid aggregation inhibitors, (ii) various in vitro measurements of their inhibitory potencies and additional biophysical analyses to investigate the mode of interactions, and (iii) determining the in vitro biological activities of the synthesised compounds in different cellular models. Overall, the easily available and functionalized vanillin and glucose modified copolymers are expected be a potential inhibitor for amyloid aggregation and could be of interest as a drug target in other human diseases. Moreover, the biological significance of perturbation of amyloid aggregation activity will be investigated for the development of better treatment of amyloidosis.

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