Laser spectroscopy of conformationally constrained alpha/beta-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 alpha/beta-peptides, Ac-L-Phe-ACPC-NHMe (alpha(L)beta(ACPC)), Ac-ACPC-L-Phe-NHMe (beta(ACPC)alpha(L)), and Ac-ACPC-D-Phe-NHMe (beta(ACPC)alpha(D)). These three molecules are close analogues of the hAla-containing alpha/beta-peptide counterparts Ac-L-Phe-beta(3)-hAla-NHMe, Ac-beta(3)-hAla-L-Phe-NHMe, and Ac-beta(3)-hAla-D-Phe-NHMe, which have been studied recently by James et al. (J. Am. Chem. Soc. 2009, 131, 6574). Incorporation of the beta-amino acid trans-2-aminocyclopentanecarboxylic acid (ACPC) constrains the beta-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 alpha/beta-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 approximately 20 kJ/mol. In alpha(L)beta(ACPC), the preference for C5 structures in the N-terminal position, combined with the strong preference for C8 structures in the beta-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 beta(ACPC)alpha(L) and beta(ACPC)alpha(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 induced by the change in chirality at the alpha-peptide chiral center.
James
William H
WH
Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, Indiana 47907-2084, USA.
Baquero
Esteban E
EE
Choi
Soo Hyuk
SH
Gellman
Samuel H
SH
Zwier
Timothy S
TS
D003198:Computer Simulation; D008956:Models, Chemical; D009842:Oligopeptides / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation; D013237:Stereoisomerism
C547798:Ac-ACPC-Phe-NHMe; D009842:Oligopeptides; D010455:Peptides