Recent advances in the modulation of amyloid protein aggregation using the supramolecular host-guest approaches.

Misfolding of proteins is associated with many incurable diseases in human beings. Understanding the process of aggregation from monomers to fibrils, the characterization of all intermediate species, and the origin of toxicity is very challenging. Extensive research including computational and experimental shed some light on these tricky phenomena. Non-covalent interactions between amyloidogenic domains of proteins play a major role in their self-assembly which can be disrupted by designed chemical tools. This will lead to the development of inhibitors of detrimental amyloid formations. In supramolecular host-guest chemistry approaches, different macrocycles function as hosts for encapsulating hydrophobic guests, i.e. phenylalanine residues of proteins, in their hydrophobic cavities via non-covalent interactions. In this way, they can disrupt the interactions between adjacent amyloidogenic proteins and prevent their self-aggregation. This supramolecular approach has also emerged as a prospective tool to modify the aggregation of several amyloidogenic proteins. In this review, we discussed recent supramolecular host-guest chemistry-based strategies for the inhibition of amyloid protein aggregation.