Design and Synthesis of 6‐O‐Phosphorylated Heparan Sulfate Oligosaccharides to Inhibit Amyloid β Aggregation. (16th June 2022)

• Record Type: Journal Article
• Authors: Uchimura, Kenji; Nishitsuji, Kazuchika; Chiu, Li‐Ting; Ohgita, Takashi; Saito, Hiroyuki; Allain, Fabrice; Gannedi, Veeranjaneyulu; Wong, Chi‐Huey; Hung, Shang‐Cheng
• Is Part Of: Chembiochem. Volume 23:Number 15(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-06-16
• Subjects: amyloid -- atomic force microscopy -- chemical synthesis -- glycosaminoglycan -- heparan sulfate; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.202200191
• Languages: English
• ISSNs: 1439-4227

Abstract

Abstract: Dysregulation of amyloidogenic proteins and their abnormal processing and deposition in tissues cause systemic and localized amyloidosis. Formation of amyloid β (Aβ) fibrils that deposit as amyloid plaques in Alzheimer's disease (AD) brains is an earliest pathological hallmark. The polysulfated heparan sulfate (HS)/heparin (HP) is one of the non‐protein components of Aβ deposits that not only modulates Aβ aggregation, but also acts as a receptor for Aβ fibrils to mediate their cytotoxicity. Interfering with the interaction between HS/HP and Aβ could be a therapeutic strategy to arrest amyloidosis. Here we have synthesized the 6‐ O ‐phosphorylated HS/HP oligosaccharides and reported their competitive effects on the inhibition of HP‐mediated Aβ fibril formation in vitro using a thioflavin T fluorescence assay and a tapping mode atomic force microscopy. Abstract : A 6‐ O ‐phosphorylated heparan sulfate tetrasaccharide was rationally designed and synthesized to inhibit heparin‐induced amyloid fibril formation of amyloid β (Aβ) in vitro . Its competitive effect was confirmed by a thioflavin T fluorescence assay and a tapping mode atomic force microscopy.