title: Inhibition of p53 Mutant Peptide Aggregation In Vitro by Cationic Osmolyte Acetylcholine Chloride.
abstract: Mutations of tumor suppressor protein p53 are present in almost about 50% of all cancers. It has been reported that the p53 mutations cause aggregation and subsequent loss of p53 function, leading to cancer progression. Here in this study we focus on the inhibitory effects of cationic osmolyte molecules acetylcholine chloride, and choline on an aggregation prone 10 amino acid p53 mutant peptide WRPILTIITL, and the corresponding wildtype peptide RRPILTIITL in vitro. The characterization tools used for this study include Thioflavin- T (ThT) induced fluorescence, transmission electron microscopy (TEM), congo red binding, turbidity, dynamic light scattering (DLS), and cell viability assays. The results show that acetylcholine chloride in micromolar concentrations significantly inhibit p53 mutant peptide aggregation in vitro, and could be promising candidate for p53 mutant/ misfolded protein aggregation inhibition.
authors.forename: Zhaolin
authors.initials: Z
authors.lastname: Chen
authors.affiliation: University of Michigan- Dearborn, Department of Mechanical Engineering, 4901, Evergreen Road, Dearborn, MI 48128. United States.
authors.forename: Mathumai
authors.initials: M
authors.lastname: Kanapathipillai
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology* / Q000633:toxicity; D002412:Cations / Q000494:pharmacology / Q000633:toxicity; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D009154:Mutation / Q000235:genetics; D009369:Neoplasms; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D066329:Protein Aggregates / Q000187:drug effects*; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D002412:Cations; D010446:Peptide Fragments; D066329:Protein Aggregates; D016159:Tumor Suppressor Protein p53; D000109:Acetylcholine
keywords: Aggregation; acetylcholine chloride; cancer; inhibition; osmolytes; p53 peptide