Laser spectroscopy of conformational constrained α/β-peptides: Ac-ACPC-Phe-NHMe and Ac-Phe-ACPC-NHMe

Single-conformation ultraviolet and infrared spectra have been recorded under the isolated molecule conditions of a supersonic expansion for three conformationally constrained α/β-peptides, Ac-L-Phe-ACPC-NHMe (α_Lβ_ACPC). Ac-ACPC-L-Phe-NHMe (β_ACPCα_L), and Ac-ACPC-D-Phe-NHMe (β_ACPCα_D)- These three molecules are close analogues of the hAla-containing α/β-peptide counterparts Ac-L-Phe-β³-hAla-NHMe, Ac-³-hAla-L-Phe-NHMe, and Ac-/β³-hAla-D-Phe-NHMe, which have been studied recently by James et al. (J. Am. Chem. Soc. 2009, 131.,6574). Incorporation of β-amino acid trans-2-aminocyclopentanecarboxylic acid (ACPC) constrains the β-peptide backbone via the cyclopentane ring, producing clear changes in the conformational preferences relative to the unconstrained analogues. The conformational control is manifested most obviously in the complete absence of C6 H-bonded rings, which were dominant in the unconstrained α/β- peptides. The most stable C6 ring structure (C6a) in the absence of the ACPC ring cannot be formed in its presence, while a secondary C6 ring (C6b) has its energy destabilized by ∼20 kJ/mol. In α_Lβ _ACPC the preference for C5 structures in the N-terminal position, combined with the strong preference for C8 structures in the β-peptide subunit, leads to the observation of two C5/C8 bifurcated double ring conformers. Both C8/C7 sequential double rings and C11 single rings are observed in β_ACPCα_L and β_ACPCα _D Here, the ACPC ring selectively stabilizes the C8a ring over other possible C8 structures. Finally, the combined evidence from IR and UV spectra lead to tentative assignments for diastereomeric pairs, exhibiting small but understandable shifts in the IR and UV spectra nduced by the change in chirality at the α-peptide chiral center.