Polyol and sugar osmolytes stabilize the molten globule state of α-lactalbumin and inhibit amyloid fibril formation

Kinetic control in amyloid polymorphism: Different agitation and solution conditions promote distinct amyloid polymorphs of alpha-synuclein

“…In our case, however, sorbitol, a small molecule polyhydric alcohol osmolyte, helped α-Syn overcome its kinetic barrier in microplate conditions. Osmolytes are preferentially excluded from the protein backbones and thus favor a compact conformation of different proteins [49,82]. For intrinsically disordered proteins, which are thermodynamically unfolded, the addition of osmolytes can either induce a partially folded structure (intramolecular interactions) or induce oligomerization (intermolecular interactions) [10,52].…”

Molecular Mechanisms of Inhibition of Protein Amyloid Fibril Formation: Evidence and Perspectives Based on Kinetic Models

“…In most cases, they inhibit the fibril formation of globular proteins with a well-defined definite native structure. Mono- and disaccharides, such as sucrose, trehalose, or glucose and polyhydric alcohols, inhibit aggregation of hen egg-white lysozyme [ 120 , 121 ], insulin [ 121 , 122 ], α-lactalbumin [ 123 ], bovine serum albumin [ 124 ], Vλ6 protein [ 125 ] by stabilizing their native state. Another well-known osmolyte, trimethylamine N-oxide (TMAO), inhibits insulin [ 126 , 127 ] fibril formation.…”