Fig. 1: Design of the β-hairpin mimics.

A Structure of Tau: schematic representation of Tau longest CNS isoform; B Schematic representation of Tau folded structure when interacting with MT⁶; C Chemical representation of Tau-MTs β-hairpin mimic compound (β-Tau); D Crystal structure of the Hsp90 N-terminal domain in complex with EC44 (PDB = 3NMQ) and schematic representation of the spatial distributions of β-strands placed at the crystal structure of the Hsp90 N-terminus (M = middle domain, N = N-terminal domain); E Primary structure of the Hsp90 N-terminal region highlighting key interaction sites according to Karagöz et al.⁴¹ β-strands in blue, helical structures in gray, strong hydrophobic interactions in red, and significant mono-amino acid interactions in green. F Chemical depiction of the designed peptides (H1, S4, S6, S7, S4^short, S7^short) and β-hairpin mimics β-Hsp90 inspired by the Tau-^NHsp90 interaction. Figure 1D was adapted from Fig. 4A of Karagoz et al. Hsp90-Tau Complex Reveals Molecular Basis for Specificity in Chaperone Action, 2014⁴¹.