title: Local control of the cis-trans isomerization and backbone dihedral angles in peptides using trifluoromethylated pseudoprolines.
abstract: NMR studies and theoretical calculations have been performed on model peptides Ac-Ser(ΨPro)-NHMe, (S,S)Ac-Ser(Ψ(H,CF3)Pro)-NHMe, and (R,S)Ac-Ser(Ψ(CF3,H)Pro)-NHMe. Their thermodynamic and kinetic features have been analyzed in chloroform, DMSO, and water, allowing a precise description of their conformational properties. We found that trifluoromethyl C(δ)-substitutions of oxazolidine-based pseudoprolines can strongly influence the cis-trans rotational barriers with only moderate effects on the cis/trans population ratio. In CHCl(3), the configuration of the CF(3)-C(δ) entirely controls the ψ-dihedral angle, allowing the stabilization of γ-turn-like or PPI/PPII-like backbone conformations. Moreover, in water and DMSO, this C(δ)-configuration can be used to efficiently constrain the ring puckering without affecting the cis/trans population ratio. Theoretical calculations have ascertained the electronic and geometric properties induced by the trifluoromethyl substituent and provided a rational understanding of the NMR observations.
authors.affiliation: Laboratoire des BioMolécules, UPMC Paris 06, Paris, France.
authors.forename: Debby
authors.initials: D
authors.lastname: Feytens
authors.forename: Grégory
authors.initials: G
authors.lastname: Chaume
authors.forename: Gérard
authors.initials: G
authors.lastname: Chassaing
authors.forename: Solange
authors.initials: S
authors.lastname: Lavielle
authors.forename: Thierry
authors.initials: T
authors.lastname: Brigaud
authors.forename: Byung Jin
authors.initials: BJ
authors.lastname: Byun
authors.forename: Young Kee
authors.initials: YK
authors.lastname: Kang
authors.forename: Emeric
authors.initials: E
authors.lastname: Miclet
mesh_terms: D008968:Molecular Conformation; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000737:chemistry*; D011392:Proline / Q000031:analogs & derivatives* / Q000737:chemistry; D011789:Quantum Theory; D013237:Stereoisomerism; D013844:Thiazoles / Q000737:chemistry*
chemical_list: D010455:Peptides; D013844:Thiazoles; C505976:pseudoproline; D011392:Proline