Pharmaceutical acetylation can modulate the amyloidogenicity of human serum albumin
Human serum albumin (HSA) is an abundant carrier protein present in the blood plasma manifesting affinity for drugs and ligands. The bindings of several drugs can cause changes in the structural conformation of HSA that may affect its function. HSA is also known to in vitro form amyloid-like aggregates with fibrillar morphology as observed under TEM. Earlier, we showed that the HSA amyloid-like aggregates display self-seeding potential and detergent stability and the dimers of HSA, which are preferable for clinical applications due to their longer circulatory life, can also form amyloid-like aggregates. As aspirin, a commonly prescribed drug, was previously documented to acetylate HSA at one of its lysine residues, here, we examined if acetylation has any effect on the in vitro amyloid-like aggregation of HSA. We show that HSA acetylated in vitro using acetylsalicylic acid manifests relatively reduced levels of amyloid-specific properties such as turbidity, thioflavin-T-positive aggregation, -sheet content and stability against an ionic detergent. Also, TEM imaging shows that the acetylated HSA forms relatively less aggregates and with smaller sizeswhereas the aggregates of HSA are more abundant and larger in sizes with fibrillar morphology which further support that acetylation can attenuate the amyloid-like aggregation of HSA.
Acetylation; Amyloid aggregates; Human serum albumin; Thioflavin-T
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