title: The Activation of Free Dipeptides Promoted by Strong Activating Agents in Water Does not Yield Diketopiperazines.
abstract: The activation of dipeptides was studied in the perspective of the abiotic formation of oligopeptides of significant length as a requirement for secondary structure formation. The formation of piperazin-2,5-diones (DKP), previously considered as a dead end when activating free dipeptides, was shown in this work to be efficiently suppressed when using strong activating agents (e.g., carbodiimides). This behaviour was explained by the fast formation of a 5(4H)-oxazolone intermediate at a rate that exceeds the time scale of the rotation of the peptide bond from the predominant trans-conformation into the cis-isomer required for DKP formation. No DKP was observed when using strong activating agents whereas phosphate mixed anhydrides or moderately activated esters were observed to predominantly yield DKP. The DKP side-reaction no longer constitutes a drawback for the C-terminus elongation of peptides. These results are considered as additional evidence that pathways involving strong activation are required to drive the emergence of living entities rather than close to equilibrium processes.
authors.affiliation: Institut des Biomolécules Max Mousseron, UMR 5247, CNRS - University of Montpellier, DSBC, CC17006, Place E. Bataillon, 34095, Montpellier Cedex 5, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Beaufils
authors.affiliation: Institut des Biomolécules Max Mousseron, UMR 5247, CNRS - University of Montpellier, DSBC, CC17006, Place E. Bataillon, 34095, Montpellier Cedex 5, France.
authors.forename: Sandra
authors.initials: S
authors.lastname: Jepaul
authors.affiliation: Institut des Biomolécules Max Mousseron, UMR 5247, CNRS - University of Montpellier, DSBC, CC17006, Place E. Bataillon, 34095, Montpellier Cedex 5, France.
authors.forename: Ziwei
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Institut des Biomolécules Max Mousseron, UMR 5247, CNRS - University of Montpellier, DSBC, CC17006, Place E. Bataillon, 34095, Montpellier Cedex 5, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Boiteau
authors.affiliation: Institut des Biomolécules Max Mousseron, UMR 5247, CNRS - University of Montpellier, DSBC, CC17006, Place E. Bataillon, 34095, Montpellier Cedex 5, France. rpascal@univ-montp2.fr.
authors.forename: Robert
authors.identifier: http://orcid.org/0000-0001-9579-2503
authors.initials: R
authors.lastname: Pascal
mesh_terms: D054659:Diketopiperazines / Q000737:chemistry*; D004151:Dipeptides / Q000737:chemistry*; D000069497:Origin of Life
chemical_list: D054659:Diketopiperazines; D004151:Dipeptides
keywords: 5(4H)-oxazolone; Activation; Diketopiperazine; Elongation; Peptide