The N-capping box is a distinct helix-stabilizing motif frequently found in proteins. In this study, we examined a ruthenium-mediated intramolecular backbone to side chain macrocyclization as a rigidified mimicry of the N-capping box. Experimental data indicate that the 15-membered macrocycle formed by a hept-4-enoyl staple, which directly tethers the α-amino group of N1 residue and the α-carbon of N3 residue, is highly effective in stabilizing helical structures of short peptides.
Keywords: N-capping box; Peptide drugs; Peptide stapling; Ring-closing metathesis; α-Helix.
Copyright © 2020 Elsevier Inc. All rights reserved.