The 1, 3‐diyne linker as a rigid "i, i+7" staple for α‐helix stabilization: Stereochemistry at work. (18th June 2019)

• Record Type: Journal Article
• Authors: Verlinden, Steven; Geudens, Niels; Van holsbeeck, Kevin; Mannes, Morgane; Martins, José C.; Verniest, Guido; Ballet, Steven
• Is Part Of: Journal of peptide science. Volume 25:Number 7(2019)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2019-06-18
• Subjects: constrained peptides -- Glaser‐Hay coupling -- helix stabilization -- peptide stapling; Peptides -- Periodicals; Peptides -- Periodicals; 572.65
• DOI: 10.1002/psc.3194
• Languages: English
• ISSNs: 1075-2617

Abstract

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.