Carbohydrate–Aromatic Interactions: Vibrational Spectroscopy and Structural Assignment of Isolated Monosaccharide Complexes with p-Hydroxy Toluene and N-Acetyl l-Tyrosine Methylamide

Abstract

The nature of carbohydrate binding first to p-hydroxy toluene and then the capped amino acid, N-acetyl l-tyrosine methyl amide (AcTyrNHMe), has been investigated in a solvent-free environment under molecular beam conditions. A combination of double resonance IR-UV spectroscopy and quantum chemical calculations has established the structures of complexes with the α and β anomers of methyl d-gluco- and d-galacto- and l-fucopyranosides (α/βMeGlc, MeGal, MeFuc). The new results, when combined with dispersion-corrected DFT calculations, reveal gas phase structures which are dominated by hydrogen bonding but also with evidence of CH-π bonded interactions in complexes with α/βMeGal. These adopt stacked intermolecular structures in marked contrast to those with α/βMeGlc; p-OH → O bonds linking AcTyrNHMe, or p-hydroxy toluene, to the carbohydrate provide an anchor that facilitates further binding, both through OH → O and NH → O hydrogen bonds to the peptide backbone and through CH-π dispersion interactions with the aromatic side group. "Stacked" structures associated with dispersion interactions with the aromatic ring are not detected in the corresponding complexes of capped phenylalanine, despite their common occurrence in bound carbohydrate-protein structures.

Isolated Neutral Peptides

“…They have been observed in model peptides based on Trp [63], Phe [70] and Tyr [114], but their occurrence requires specific stabilisation conditions because of the intrinsic weakness of the H-bond caused by its nonlinearity, in spite of a short H-O distance (228 pm). They are usually challenged by the other short range, but much stronger, C7 H-bonds, which lead in turn to folded backbone structures [63,70,73,83,114,188,191]. In esterified C-terminal models [46,87], the absence of an NH group forbids the folded structures.…”

“…In addition, the folding from the NH of the second Ala residue into a C7 H-bond is hampered by significant entropic effects which favour extended forms because of their multiple low frequency modes. Amidated models, [63,70,73,83,114] as well as di-or tri-peptides with Phe or Trp as first residue [84,85,94,104,112], have also revealed C5-containing secondary structures. In these conformations, the C5 H-bond occurring at the aromatic residue is additionally stabilised by an interaction between the π system of the aromatic ring and the NH of the following residue along the chain , making the 5-π motif very common among these secondary structures.…”

“…They are quite easily observed in the gas phase, in capped amino-acids [63,70,73,83,114,131,188], or often in combination with other secondary structures, for instance following an extended Phe residue with a C5 interactions leading to 5-π-7 structures [70,84,85,94,112] (Fig. 4).…”

“…Beyond microsolvation, peptide-peptide interactions [31,46,73,87,90,120,124] and complexation with larger molecules have also been considered by several groups, especially to describe specifically interesting interactions between a peptide and its biological environment: peptides have been complexed with pyrazole to 246 E. Gloaguen and M. Mons favour β-sheets [65,100], with sugars to describe the interactions responsible for cellular recognition in glycopeptides [114,197], or to document the anomeric effect [198].…”

Phenyl-β-D-glucopyranoside and Phenyl-β-D-galactopyranoside Dimers: Small Structural Differences but Very Different Interactions

“…Note that the only difference between both monosacharides is the relative position of the O4H hydroxyl group. such as amino acids or peptides [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21], neurotransmitters [22][23][24][25][26][27][28], anesthetics [29,30], several mono-, di-and poly-saccharides [4,6,[31][32][33][34][35][36][37][38][39] or even micelles [40][41][42]. In these systems, the addition of a chromophore with an optically accessible excited electronic state is required to probe the molecules.…”