Supercharging Prions via Amyloid‐Selective Lysine Acetylation

نویسندگان

چکیده

Abstract Repulsive electrostatic forces between prion‐like proteins are a barrier against aggregation. In neuropharmacology, however, prion's net charge ( Z ) is not targeted parameter. Compounds that selectively boost prion remain unreported. Here, we synthesized compounds amplified the negative of misfolded superoxide dismutase‐1 (SOD1) by acetylating lysine‐NH 3 + in amyloid‐SOD1, without native‐SOD1. resembled “ball and chain” mace: rigid amyloid‐binding “handle” (benzothiazole, stilbene, or styrylpyridine); an aryl ester “ball”; triethylene glycol chain connecting ball to handle. At stoichiometric excess, acetylated up 9 11 lysine per subunit (Δ fibril =−8100 10 subunits). Acetylated amyloid‐SOD1 seeded aggregation more slowly than unacetylated vitro organotypic spinal cord (these effects were partially due compound binding). exhibited reactivity with other amyloid non‐amyloid (e.g., fibrillar α‐synuclein was peracetylated; serum albumin acetylated; carbonic anhydrase largely unacetylated).

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ژورنال

عنوان ژورنال: Angewandte Chemie

سال: 2021

ISSN: ['1521-3773', '1433-7851', '0570-0833']

DOI: https://doi.org/10.1002/anie.202103548