title: Infrared Probe Technique Reveals a Millipede-like Structure for Aβ(8-28) Amyloid Fibril.
abstract: Amyloid fibrils are unique fibrous polypeptide aggregates. They have been associated with more than 20 serious human diseases including Alzheimer's disease and Parkinson's disease. Besides their pathological significance, amyloid fibrils are also gaining increasing attention as emerging nanomaterials with novel functions. Structural characterization of amyloid fibril is no doubt fundamentally important for the development of therapeutics for amyloid-related diseases and for the rational design of amyloid-based materials. In this study, we explored to use side-chain-based infrared (IR) probe to gain detailed structural insights into the amyloid fibril by a 21-residue model amyloidogenic peptide, Aβ(8-28). We first proposed an approach to incorporate thiocyanate (SCN) IR probe in a site-specific manner into amyloidogenic peptide using 1-cyano-4-dimethylaminopyridinium tetrafluoroborate as cyanylating agent. Using this approach, we obtained three Aβ(8-28) variants, labeled with SCN probe at three different positions. We then showed with thioflavin T fluorescence assay, Congo red assay, and atomic force microscopy that the three labeled Aβ(8-28) peptides can quickly form amyloid fibrils under high concentration and high salt conditions. Finally, we performed a detailed IR spectral analysis of the Aβ(8-28) fibril in both amide I and probe regions and proposed a millipede-like structure for the Aβ(8-28) fibril.
authors.affiliation: Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, Key Laboratory of Analytical Science and Technology of Hebei Province, College of Chemistry and Environmental Science, Hebei University , Baoding 071002, China.
authors.forename: Yachao
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, Key Laboratory of Analytical Science and Technology of Hebei Province, College of Chemistry and Environmental Science, Hebei University , Baoding 071002, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Zou
authors.affiliation: Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, Key Laboratory of Analytical Science and Technology of Hebei Province, College of Chemistry and Environmental Science, Hebei University , Baoding 071002, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, Key Laboratory of Analytical Science and Technology of Hebei Province, College of Chemistry and Environmental Science, Hebei University , Baoding 071002, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.affiliation: Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, Key Laboratory of Analytical Science and Technology of Hebei Province, College of Chemistry and Environmental Science, Hebei University , Baoding 071002, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, Key Laboratory of Analytical Science and Technology of Hebei Province, College of Chemistry and Environmental Science, Hebei University , Baoding 071002, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Ma
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry*; D009570:Nitriles / Q000737:chemistry; D010446:Peptide Fragments / Q000737:chemistry*; D020836:Protein Structure, Quaternary; D011726:Pyridinium Compounds / Q000737:chemistry; D013055:Spectrophotometry, Infrared
chemical_list: D016229:Amyloid beta-Peptides; D009570:Nitriles; D010446:Peptide Fragments; D011726:Pyridinium Compounds; C000613707:amyloid beta-peptide(8-28); C067292:1-cyano-4-dimethylaminopyridinium