The 1, 3‐diyne linker as a rigid "i, i+7" staple for α‐helix stabilization: Stereochemistry at work. (18th June 2019) - Verlinden, Steven
Abstract : Short alphahelical peptide sequences were stabilized through Glaser‐Hay couplings of propargylated l ‐ and/or d ‐serine residues at positions i and i +7. NMR analysis confirmed a full stabilization of the helical structure when a d ‐Ser (i), l ‐Ser ( i +7) combination was applied. In case two l ‐Ser residues were involved in the cyclization, the helical conformation is disrupted outside the peptide's macrocycle. Abstract : Alpha‐helix stabilization by means of 1, 3‐diyne stapling is efficient when a combination of side chain propargylated d ‐ and l ‐Ser residues is deployed in positions i and i +7, respectively. Structure analysis via NMR and molecular modeling proved that the [l ‐Ser4, l ‐Ser11] combination only provided a helical structure within the macrocycle, while the exocyclic segment was not part of the helix.