title: Selective Inhibition of Aggregation and Toxicity of a Tau-Derived Peptide using Its Glycosylated Analogues.
abstract: Protein glycosylation is a ubiquitous post-translational modification that regulates the folding and function of many proteins. Misfolding of protein monomers and their toxic aggregation are the hallmark of many prevalent diseases. Thus, understanding the role of glycans in protein aggregation is highly important and could contribute both to unraveling the pathology of protein misfolding diseases as well as providing a means for modifying their course for therapeutic purposes. Using β-O-linked glycosylated variants of the highly studied Tau-derived hexapeptide motif VQIVYK, which served as a simplified amyloid model, we demonstrate that amyloid formation and toxicity can be strongly attenuated by a glycan unit, depending on the nature of the glycan itself. Importantly, we show for the first time that not only do glycans hinder self-aggregation, but the glycosylated peptides are capable of inhibiting aggregation of the non-modified corresponding amyloid scaffold.
authors.affiliation: Department Molecular Microbiology and Biotechnology, and the Interdisciplinary Sagol School of Neurosciences, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Tel Aviv, 69978, Israel.
authors.forename: Moran
authors.initials: M
authors.lastname: Frenkel-Pinter
authors.affiliation: Department of Chemistry, Bar-Ilan University, Ramat-Gan, 5290002, Israel.
authors.forename: Michal
authors.initials: M
authors.lastname: Richman
authors.affiliation: Department of Chemistry, Bar-Ilan University, Ramat-Gan, 5290002, Israel.
authors.forename: Anna
authors.initials: A
authors.lastname: Belostozky
authors.affiliation: Department Molecular Microbiology and Biotechnology, and the Interdisciplinary Sagol School of Neurosciences, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Tel Aviv, 69978, Israel.
authors.forename: Amjaad
authors.initials: A
authors.lastname: Abu-Mokh
authors.affiliation: Department Molecular Microbiology and Biotechnology, and the Interdisciplinary Sagol School of Neurosciences, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Tel Aviv, 69978, Israel. dsegal@post.tau.ac.il.
authors.forename: Ehud
authors.initials: E
authors.lastname: Gazit
authors.affiliation: Department of Chemistry, Bar-Ilan University, Ramat-Gan, 5290002, Israel. rahimis@biu.ac.il.
authors.forename: Shai
authors.initials: S
authors.lastname: Rahimipour
authors.affiliation: Department Molecular Microbiology and Biotechnology, and the Interdisciplinary Sagol School of Neurosciences, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Tel Aviv, 69978, Israel. ehudg@post.tau.ac.il.
authors.forename: Daniel
authors.initials: D
authors.lastname: Segal
mesh_terms: D000595:Amino Acid Sequence; D000682:Amyloid / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D009842:Oligopeptides / Q000737:chemistry* / Q000378:metabolism; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D017433:Protein Structure, Secondary; D016875:tau Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000682:Amyloid; D009842:Oligopeptides; D010455:Peptides; D016875:tau Proteins
keywords: PHF6; amyloid formation; glycopeptides; glycosylation; protein and peptide aggregation