title: Inhibition and Degradation of Amyloid Beta (Aβ40) Fibrillation by Designed Small Peptide: A Combined Spectroscopy, Microscopy, and Cell Toxicity Study.
abstract: A designed nontoxic, nonhemolytic 11-residue peptide, NF11 (NAVRWSLMRPF), not only inhibits the aggregation of amyloid beta (Aβ40) protein but also disaggregates the preformed oligomers and mature Aβ fibrils, thereby reducing associated-toxicity. NMR experiments provide evidence of NF11's ability to inhibit fibril formation, primarily through interaction with the N-terminus region as well as the central hydrophobic cluster of Aβ40. NF11 has micromolar binding affinity toward both monomeric and aggregated species for efficient clearance of toxic aggregates. From these in vitro results, the future development of a next generation peptidomimetic therapeutic agent for amyloid disease may be possible.
authors.affiliation: Department of Biophysics, Bose Institute , Kolkata 700054, India.
authors.forename: Anirban
authors.initials: A
authors.lastname: Ghosh
authors.affiliation: Indian Association for the Cultivation of Science , Kolkata 700032, India.
authors.forename: Nibedita
authors.initials: N
authors.lastname: Pradhan
authors.affiliation: Department of Biophysics, Bose Institute , Kolkata 700054, India.
authors.forename: Swapna
authors.initials: S
authors.lastname: Bera
authors.affiliation: Department of Biophysics, Bose Institute , Kolkata 700054, India.
authors.forename: Aritreyee
authors.initials: A
authors.lastname: Datta
authors.affiliation: Vclinbio Laboratories Pvt Ltd., Sri Ramachandra Medical Center , Chennai 600116, India.
authors.forename: Janarthanan
authors.initials: J
authors.lastname: Krishnamoorthy
authors.affiliation: Indian Association for the Cultivation of Science , Kolkata 700032, India.
authors.forename: Nikhil R
authors.identifier: 0000-0002-4595-6917
authors.initials: NR
authors.lastname: Jana
authors.affiliation: Department of Biophysics, Bose Institute , Kolkata 700054, India.
authors.forename: Anirban
authors.identifier: 0000-0002-8752-2842
authors.initials: A
authors.lastname: Bhunia
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D009474:Neurons / Q000187:drug effects; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*; D010446:Peptide Fragments / Q000737:chemistry* / Q000494:pharmacology*; D066263:Protein Aggregation, Pathological / Q000188:drug therapy*
chemical_list: D016229:Amyloid beta-Peptides; C000617982:NF11 peptide; D009842:Oligopeptides; D010446:Peptide Fragments
keywords: Alzheimer’s disease; STD NMR; amyloid beta (Aβ); fibril disintegration; peptide; toxicity inhibitor