Fig. 1: Rational design of dimeric helix-hairpin.
From: A dimeric proteomimetic prevents SARS-CoV-2 infection by dimerizing the spike protein
a, Sequence and secondary structure map of LCB1. b, Cryo-EM structure of SARS-CoV-2 RBD in complex with LCB1 (7JZU). Helices 1 and 2 make direct contact with the RBD of SARS-CoV-2 and helix 3 (magenta) stabilizes LCB1 by packing against helices 1 and 2 (yellow). c, Removal of helix 3 exposes the hydrophobic residues at g positions in helices 1 and 2 (dark gray) and increases the width of the hydrophobic face. The hydrophobic residues (I12 and L31) that are substituted to obtain SIH-14 and SIH-15 are shown. The figure was generated using Pymol. d, Sequences, helicity, thermal stability and potency of the helix-hairpin peptides. The modified residues in the loop and helix are highlighted in red and green, respectively. Structure of unnatural amino acids: d-alanine (a), aminoisobutyric acid (B), 3,4-difluoro-l-phenylalanine (O) and l-cyclohexylalanine (Z). The midpoint of thermal transitions (TM) represents mean values ± s.d. derived from three independent experiments. (Helicity was measured at 20 °C in sodium-phosphate buffer, pH 7.4).
