Chiral and Molecular Recognition through Protonation between Aromatic Amino Acids and Tripeptides Probed by Collision-Activated Dissociation in the Gas Phase.

Akimasa Fujihara,Yoshinao Wada,Michiko Tajiri,Hikaru Inoue,Masanobu Sogi

doi:10.3390/molecules23010162

Abstract

Chiral and molecular recognition through protonation was investigated through the collision-activated dissociation (CAD) of protonated noncovalent complexes of aromatic amino acid enantiomers with l-alanine- and l-serine-containing tripeptides using a linear ion trap mass spectrometer. In the case of l-alanine-tripeptide (AAA), NH3 loss was observed in the CAD of heterochiral H+(d-Trp)AAA, while H2O loss was the main dissociation pathways for l-Trp, d-Phe, and l-Phe. The protonation site of heterochiral H+(d-Trp)AAA was the amino group of d-Trp, and the NH3 loss occurred from H+(d-Trp). The H2O loss indicated that the proton was attached to the l-alanine tripeptide in the noncovalent complexes. With the substitution of a central residue of l-alanine tripeptide to l-Ser, ASA recognized l-Phe by protonation to the amino group of l-Phe in homochiral H+(l-Phe)ASA. For the protonated noncovalent complexes of His enantiomers with tripeptides (AAA, SAA, ASA, and AAS), protonated His was observed in the spectra, except for those of heterochiral H+(d-His)SAA and H+(d-His)AAS, indicating that d-His did not accept protons from the SAA and AAS in the noncovalent complexes. The amino-acid sequences of the tripeptides required for the recognition of aromatic amino acids were determined by analyses of the CAD spectra.

Highlights

Biomolecules have the ability to recognize chiral molecules
Enantiomeric separation is crucial in chemistry, because one enantiomer of a chiral drug may be toxic to biological systems, while another is medically effective. Analytical techniques such as high-performance liquid chromatography, capillary electrophoresis, gas chromatography, nuclear magnetic resonance (NMR) spectroscopy, X-ray crystallography, and circular dichroism are used to distinguish between the enantiomers of chiral molecules [1,2,3,4]
We examined chiral and molecular recognition based on protonation between aromatic amino acids and L-alanine- and L-serine-containing tripeptides through the collision-activated dissociation (CAD) of gas-phase protonated noncovalent complexes between aromatic amino acids and peptides

Summary

Introduction

Enantiomeric separation is crucial in chemistry, because one enantiomer of a chiral drug may be toxic to biological systems, while another is medically effective. Analytical techniques such as high-performance liquid chromatography, capillary electrophoresis, gas chromatography, nuclear magnetic resonance (NMR) spectroscopy, X-ray crystallography, and circular dichroism are used to distinguish between the enantiomers of chiral molecules [1,2,3,4]. The chiral differentiation of amino acids by the ion mobility mass spectrometry [10,11,12] and NMR spectroscopy of gas-phase ions using magnetic resonance acceleration [13,14] has been reported.

Methods

Results

Conclusion