Intramolecular recognition in a jet-cooled short peptide chain: γ-turn helicity probed by a neighbouring residue

Abstract

gamma-Turn, the shortest secondary structure of peptides, exists as two helical forms gamma(l) and gamma(d) of opposite handedness. The present gas phase study of capped l-Phe-Xxx peptides (Xxx = l-Ala, d-Ala or Aib: aminoisobutyric acid) provides a unique example of intramolecular chiral recognition of the gamma-turn helicity on Ala or Aib by the neighbouring residue Phe within the chain. With the chiral l- or d-Ala residues, the presence of a side-chain operates a discrimination between the two helical forms: one of them is widely favoured over the other (gamma(l) or gamma(d), respectively). This enables us to validate and calibrate the recognition capabilities of the nearby l-Phe residue. The discriminating interactions have been precisely characterized from their spectroscopic UV and IR signatures and identified by comparison with quantum chemistry calculations. Then, in the case of the non-chiral residue Aib, the two helical forms of the gamma-turn, which are simultaneously observed in the jet, have been discriminated and assigned by comparison with the chiral residues. The relative abundances of the diastereomeric forms l-Phe-Aib(gamma(l)) and l-Phe-Aib(gamma(d)) enable us to determine the most efficient recognition configuration.

Effect of the Chirality of Residues and γ‐Turns on the Electronic Excitation Spectra, Excited‐State Reaction Paths and Conical Intersections of Capped Phenylalanine–Alanine Dipeptides

“…Although the C 7 eq structures are energetically favored relative to the C 7 ax structures (see Table 1), they possess the longer (and thus weaker) hydrogen bond of the g-turn (see Table 2). These findings agree with the results of Gloaguen et al [24] …”

“…Both conformers were observed in the resonant multi-photon ionization (REMPI) spectra and were assigned via their UV and IR spectra. [24] B. Ac-l-Phe-d-Ala-NH 2 Two bands, one strong and one weak, were observed in the REMPI spectrum of this species. [24] By the analysis of the IR spectrum, the strong band (corresponding to the most abundant conformer in the jet) was assigned as the g D structure (see Figure 1 b) by Gloaguen et al The weak band was tentatively assigned to the g L structure (see Figure 1 b).…”

“…The MP2 calculations predict the g D structure to be lower in energy than the g L structure, see Table 1. The relative energies are determined by the interplay of the C 7 H-bond (C 7 ax bonds tend to be stronger than C 7 eq bonds), the contacts between the methyl group of Ala with the phenyl ring, as well as NH···p interactions, as discussed by Gloaguen et al [24] C. Ac-l-Phe-l-Ala-NH 2 The g D and g L conformers of this species are shown in Figure 1 c. In this case, the MP2 calculations predict the g L structure to be lower in energy than the g D structure, see Table 1. The REMPI spectrum exhibits a single band which was assigned to the g L conformer via the analysis of its IR spectrum.…”

Chirality Recognition between Neutral Molecules in the Gas Phase

“…Zehnacker and M. A. Suhm Reviews tion or folding properties [167] are just secondary effects. These effects have been demonstrated in some recent spectroscopic peptide studies [166,167] but many other examples could be mentioned in this context. [129,168] A detailed discussion of the formation of stereotactic polymers through chirality induction is beyond the scope of this Review.…”

“…A small variant is the g-turn, which can even be established in a capped dipeptide in the gas phase. [166] If only one of the amino acids is chiral, the g-turn exists in two helicities which are simultaneously observed. However, a specific helicity of the g-turn is preferred.…”