Glaser oxidative coupling on peptides: stabilization of β-turn structure via a 1,3-butadiyne constraint

Nicolas Auberger; Margherita Di Pisa; Maud Larregola; Gérard Chassaing; Elisa Peroni; Solange Lavielle; Anna-Maria Papini; Olivier Lequin; Jean-Maurice Mallet

doi:10.1016/j.bmc.2014.10.026

Glaser oxidative coupling on peptides: stabilization of β-turn structure via a 1,3-butadiyne constraint

Bioorg Med Chem. 2014 Dec 15;22(24):6924-32. doi: 10.1016/j.bmc.2014.10.026. Epub 2014 Oct 22.

Authors

Nicolas Auberger¹, Margherita Di Pisa², Maud Larregola³, Gérard Chassaing¹, Elisa Peroni³, Solange Lavielle¹, Anna-Maria Papini³, Olivier Lequin¹, Jean-Maurice Mallet¹

Affiliations

¹ École Normale Supérieure-PSL Research University, Département de Chimie, 24, rue Lhomond, 75005 Paris, France; Sorbonne Universités, UPMC Univ Paris 06, LBM, 4 place Jussieu, F-75005 Paris, France; CNRS, UMR 7203 LBM, F-75005 Paris, France.
² École Normale Supérieure-PSL Research University, Département de Chimie, 24, rue Lhomond, 75005 Paris, France; Sorbonne Universités, UPMC Univ Paris 06, LBM, 4 place Jussieu, F-75005 Paris, France; CNRS, UMR 7203 LBM, F-75005 Paris, France; PeptLab-SOSCO EA4505 University of Florence Via della Lastruccia 13, I-50019 Sesto F.no, Italy and University of Cergy-Pontoise, 5 Mail Gay Lussac, F-95031 Cergy-Pontoise CEDEX, France.
³ PeptLab-SOSCO EA4505 University of Florence Via della Lastruccia 13, I-50019 Sesto F.no, Italy and University of Cergy-Pontoise, 5 Mail Gay Lussac, F-95031 Cergy-Pontoise CEDEX, France.

PMID: 25456082
DOI: 10.1016/j.bmc.2014.10.026

Abstract

The Glaser-Eglinton reaction between either two C or N propargylglycine (Pra or NPra) amino acids, in the presence of copper(II), led to cyclic hexa- and octapeptides constrained by a butadiyne bridge. The on-resin cyclization conditions were analyzed and optimized. The consequences of this type of constraint on the three dimensional structure of these hexapeptides and octapeptides were analyzed in details by NMR and molecular dynamics. We show that stabilized short cyclic peptides could be readily prepared via the Glaser oxidative coupling either with a chiral (Pra), or achiral (NPra) residue. The 1,3-butadiyne cyclization, along with disulfide bridged and lactam cyclized hexapeptides expands the range of constrained peptides that will allow exploring the breathing of amino acids around a β-turn structure.

Keywords: Constraint; Glaser oxidative coupling; NMR studies; Peptides; β-Turn structure.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alkynes / chemistry*
Amino Acid Sequence
Copper / chemistry
Magnetic Resonance Spectroscopy
Molecular Dynamics Simulation
Oxidative Coupling
Peptides, Cyclic / chemical synthesis
Peptides, Cyclic / chemistry*
Protein Structure, Secondary

Substances

Alkynes
Peptides, Cyclic
Copper