12/14/14-Helix Formation in 2:1 α/β-Hybrid Peptides Containing Bicyclo[2.2.2]octane Ring Constraints.
The highly constrained β-amino acid ABOC induces different types of helices in β urea and 1:1 α/β amide oligomers. The latter can adopt 11/9- and 18/16-helical folds depending on the chain length in solution. Short peptides alternating proteinogenic α-amino acids and ABOC in a 2:1 α/β repeat pattern adopted an unprecedented and stable 12/14/14-helix. The structure was established through extensive NMR, molecular dynamics, and IR studies. While the 1:1 α-AA/ABOC helices diverged from the canonical α-helix, the helix formed by the 9-mer 2:1 α/β-peptide allowed the projection of the α-amino acid side chains in a spatial arrangement according to the α-helix. Such a finding constitutes an important step toward the conception of functional tools that use the ABOC residue as a potent helix inducer for biological applications.
Institut des Biomolécules Max Mousseron (IBMM), UMR 5247 CNRS-Université Montpellier-ENSCM, 15 avenue Charles Flahault, 34093, Montpellier, cedex 5, France.
Baptiste
B
Legrand
Institut des Biomolécules Max Mousseron (IBMM), UMR 5247 CNRS-Université Montpellier-ENSCM, 15 avenue Charles Flahault, 34093, Montpellier, cedex 5, France.
Christophe
C
André
Institut des Biomolécules Max Mousseron (IBMM), UMR 5247 CNRS-Université Montpellier-ENSCM, 15 avenue Charles Flahault, 34093, Montpellier, cedex 5, France.
Laure
L
Moulat
CRM2, UMR 7063 CNRS Université de Lorraine, Boulevard des Aiguilletes, 54506, Vandoeuvre-lès-Nancy, Cedex, France.
Claude
C
Didierjean
Institut Charles Gerhardt Montpellier, UMR-5253, CNRS, Université de Montpellier, ENSCM, Place E. Bataillon, 34095, Montpellier, Cédex 5, France.
Patrick
P
Hermet
Laboratoire Charles Coulomb, UMR 5221 CNRS-Université de Montpellier, 34095, Montpellier, France.
Jean-Louis
JL
Bantignies
Institut des Biomolécules Max Mousseron (IBMM), UMR 5247 CNRS-Université Montpellier-ENSCM, 15 avenue Charles Flahault, 34093, Montpellier, cedex 5, France.
Jean
J
Martinez
Institut des Biomolécules Max Mousseron (IBMM), UMR 5247 CNRS-Université Montpellier-ENSCM, 15 avenue Charles Flahault, 34093, Montpellier, cedex 5, France. muriel.amblard@univ-montp1.fr.
Muriel
M
Amblard
Institut des Biomolécules Max Mousseron (IBMM), UMR 5247 CNRS-Université Montpellier-ENSCM, 15 avenue Charles Flahault, 34093, Montpellier, cedex 5, France. monique.calmes@univ-montp2.fr.
Monique
M
Calmès
D000577:Amides / Q000737:chemistry*; D000596:Amino Acids / Q000737:chemistry*; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D009795:Octanes / Q000737:chemistry*; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry*; D017433:Protein Structure, Secondary; D014508:Urea / Q000737:chemistry*
D000577:Amides; D000596:Amino Acids; D001643:Bridged Bicyclo Compounds; D009795:Octanes; D010455:Peptides; D014508:Urea
12/14/14-helix; bicyclic β-amino acids; helical structures; structure elucidation; α/β-hybrid peptides