Accurate Characterization of the Peptide Linkage in the Gas Phase: A Joint Quantum-Chemical and Rotational Spectroscopy Study of the Glycine Dipeptide Analogue

Abstract

Accurate structures of aminoacids in the gas phase have been obtained by joint microwave and quantum-chemical investigations. However, the structure and conformational behavior of α-aminoacids once incorporated into peptide chains are completely different and have not yet been characterized with the same accuracy. To fill this gap, we present here an accurate characterization of the simplest dipeptide analogue (N-acetyl-glycinamide) involving peptidic bonds. State-of-the-art quantum-chemical computations are complemented by a comprehensive study of the rotational spectrum using a combination of Fourier transform microwave spectroscopy with laser ablation. The coexistence of the C7 and C5 conformers has been proved and energetically as well as spectroscopically characterized. This joint theoretical-experimental investigation demonstrated the feasibility of obtaining accurate structures for flexible small biomolecules, thus paving the route to the elucidation of the inherent behavior of peptides.

Noncovalent Interactions and Internal Dynamics in Pyridine–Ammonia: A Combined Quantum‐Chemical and Microwave Spectroscopy Study

“…A composite scheme analogous to that used for the structural determination was employed for accurate prediction of the equilibrium nuclear quadrupole‐coupling constants of both nitrogen atoms (one belonging to PYR and one to NH 3 ) . Subsequently, the ground‐state quadrupole‐coupling constants were obtained by correcting the best‐estimated equilibrium values through vibrational contributions evaluated at the B2PLYP‐D3/ m ‐aug‐cc‐pVTZ‐ d H level…”

Fourier transform microwave spectroscopy of Ac-Ser-NH2: the role of side chain interactions in peptide folding

“…Lavrich et al 6 investigated the alanine dipeptide N-acetyl-alanine N 0 -methylamide (Ac-Ala-NHMe) and observed only a C eq 7 conformation using heating methods to bring molecules into the gas phase. Very recently, the combination of FTMW spectroscopic techniques with laser ablation methods [7][8][9][10] has been successfully applied in the investigation of the conformational preferences of isolated protected dipeptides such as N-acetyl-glycinamide (Ac-Gly-NH 2 ), 11 N-acetyl-alaninamide (Ac-Ala-NH 2 ) 12 and N-acetyl-prolinamide (Ac-Pro-NH 2 ). 13 For both Ac-Gly-NH 2 and Ac-Ala-NH 2 , the molecules were found to exist as both the C eq 7 (g-turn) as well as the C 5 (b L -turn) conformation (see Scheme 1), in which the backbones are stabilized by a COÁ Á ÁHN intramolecular hydrogen bond closing a seven-or five-membered ring, respectively.…”

Accurate molecular structures of small‐ and medium‐sized molecules

“…The question is here whether more flexible systems as well as molecular complexes can be accurately and effectively described as well. A positive answer comes, for example, from a recent work concerning the structural and spectroscopic investigation of the simplest dipeptide analogue, N ‐acetylglycinamide …”

“…In reference , the so‐defined “cheap geometry” scheme was employed to provide accurate prediction of the spectroscopic parameters of relevance in the assignment of the rotational spectrum of N ‐acetylglycinamide. As confirmed by experiment, two conformers were found to be stable in gas‐phase: the C 5 and C 7 conformers, with the latter being the most stable by about 200 cm –1 .…”

“…As confirmed by experiment, two conformers were found to be stable in gas‐phase: the C 5 and C 7 conformers, with the latter being the most stable by about 200 cm –1 . The reader is referred to reference for all details. Of relevance to this study is the determination of the rotational and nitrogen‐quadrupole coupling constants.…”