title: Synthesis and evaluation of ferrocenoyl pentapeptide (Fc-KLVFF) as an inhibitor of Alzheimer's Aβ₁-₄₂ fibril formation in vitro.
abstract: Aggregation and fibril formation of β-amyloid peptides (Aβ) is the key event in the pathogenesis of Alzheimer's disease. Many efforts have been made on the development of effective inhibitors to prevent Aβ fibril formation or disassemble the preformed Aβ fibrils. Peptide inhibitors with sequences homologous to the hydrophobic segments of Aβ can alter the aggregation pathway of Aβ, together with decrease of the cell toxicity. In this study, the conjugate of ferrocenoyl (Fc) with pentapeptide KLVFF (Fc-KLVFF), was synthesized by HBTU/HOBt protocol in solution. The inhibitory effect of Fc-KLVFF on Aβ(1-42) fibril formation was evaluated by thioflavin T fluorescence assay, and confirmed by atomic force microscopy (AFM) and transmission electron microscopy (TEM) analyses. Fc-KLVFF shows high inhibitory effect towards the fibril formation of Aβ(1-42). Additionally, the attachment of ferrocenoyl moiety onto peptides allows us to investigate the interaction between the inhibitor and Aβ(1-42) in real-time by electrochemical method. As expected, tethering of ferrocenoyl moiety onto pentapeptide shows improved lipophilicity and significant resistance towards proteolytic degradation compared to its parent peptide.
authors.affiliation: College of Chemistry and Chemical Engineering, Central South University, Changsha, Hunan 410083, PR China.
authors.forename: Chuan-Wan
authors.initials: CW
authors.lastname: Wei
authors.forename: Yong
authors.initials: Y
authors.lastname: Peng
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.forename: Qiyu
authors.initials: Q
authors.lastname: Huang
authors.forename: Ming
authors.initials: M
authors.lastname: Cheng
authors.forename: You-Nian
authors.initials: YN
authors.lastname: Liu
authors.forename: Juan
authors.initials: J
authors.lastname: Li
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism*; D052160:Benzothiazoles; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D055664:Electrochemical Techniques; D005290:Ferric Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D018625:Microscopy, Atomic Force; D046529:Microscopy, Electron, Transmission; D058990:Molecular Targeted Therapy; D018697:Nootropic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry; D012995:Solubility; D013844:Thiazoles / Q000737:chemistry
chemical_list: D016229:Amyloid beta-Peptides; D052160:Benzothiazoles; C571358:Fc-KLVFF; D005290:Ferric Compounds; D018697:Nootropic Agents; D009842:Oligopeptides; D010446:Peptide Fragments; D010455:Peptides; D013844:Thiazoles; C075222:amyloid beta-protein (1-42); C529399:amyloid beta-protein (16-20); C009462:thioflavin T