Helix stabilization by stapled N-capping box

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 alpha-amino group of N1 residue and the alpha-carbon of N3 residue, is highly effective in stabilizing helical structures of short peptides.