The 1,3-diyne linker as a rigid "i,i+7" staple for α-helix stabilization: Stereochemistry at work

Steven Verlinden; Niels Geudens; Kevin Van Holsbeeck; Morgane Mannes; José C Martins; Guido Verniest; Steven Ballet

doi:10.1002/psc.3194

The 1,3-diyne linker as a rigid "i,i+7" staple for α-helix stabilization: Stereochemistry at work

J Pept Sci. 2019 Jul;25(7):e3194. doi: 10.1002/psc.3194. Epub 2019 Jun 18.

Authors

Steven Verlinden¹, Niels Geudens², Kevin Van Holsbeeck^{1

2}, Morgane Mannes¹, José C Martins², Guido Verniest^{1

3}, Steven Ballet¹

Affiliations

¹ Research Group of Organic Chemistry, Department of Chemistry and Department of Bioengineering Sciences, Faculty of Sciences and Bioengineering Sciences, Vrije Universiteit Brussel, Brussels, Belgium.
² NMR and Structure Analysis Unit, Department of Organic and Macromolecular Chemistry, Ghent University, Ghent, Belgium.
³ Predictive Analytics and Stability Sciences, Center of Excellence, CRS, Analytical Development, PDMS, DPDS, Janssen Research and Development, Janssen Pharmaceutical Companies of Johnson & Johnson, Beerse, Belgium.

PMID: 31215108
DOI: 10.1002/psc.3194

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.

Keywords: Glaser-Hay coupling; constrained peptides; helix stabilization; peptide stapling.

MeSH terms

Amino Acid Sequence
Diynes / chemistry*
Peptides / chemistry*
Protein Conformation, alpha-Helical
Protein Stability
Stereoisomerism

Substances

Diynes
Peptides

Abstract

MeSH terms

Substances

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