A simple model system for the study of carbohydrate--aromatic interactions.

Universita' di Milano, Dipartimento di Chimica Organica e Industriale e Centro di Eccellenza CISI, via Venezian 21, 20133 Milano, Italy.
Journal of the American Chemical Society (Impact Factor: 11.44). 04/2007; 129(10):2890-900. DOI: 10.1021/ja066633g
Source: PubMed

ABSTRACT A molecular scaffold was identified which enables the establishment of intramolecular interactions between a monosaccharide and a nearby phenyl ring. A group of molecules containing four different monosaccharides (glucose, galactose, N-acetyl-glucosamine, and N-acetyl-galactosamine) was synthesized and used to investigate the extent and nature of this carbohydrate-arene interaction, as well as the effect on the overall 3D structure of the molecules involved. The sugar-aromatic distance was evaluated by rigorous NMR studies supported by molecular modeling and found to be constant throughout the series, independent of the nature of the sugar and of the conformational behavior of the fragment connecting the two elements. Ab initio calculations at the B3LYP/DZV(2d,p) level of theory enable the analysis of the electronic nature of the interaction. The study shows that, given the opportunity, persistent intramolecular aromatic-sugar interactions can be established and can significantly influence overall molecular shape and energetics. These results have important implications in the design of structural mimics of oligosaccharides.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Engineering of novel carbohydrate-binding proteins that can be utilized in various biochemical and biotechnical applications would benefit from a deeper understanding of the biochemical interactions that determine protein-carbohydrate specificity. In an effort to understand further the basis for specificity we present the crystal structure of the multi-specific carbohydrate-binding module (CBM) X-2 L110F bound to a branched oligomer of xyloglucan (XXXG). X-2 L110F is an engineered CBM that can recognize xyloglucan, xylans and β-glucans. The structural observations of the present study compared with previously reported structures of X-2 L110F, in complex to linear oligomers, show that the π-surface of a phenylalanine, F110, allows for interactions with hydrogen atoms on both linear (xylopentaose and cellopentaose) and branched ligands (XXXG). Furthermore, X-2 L110F is shown to have a relatively flexible binding-cleft, as illustrated in binding to XXXG. This branched ligand requires a set of reorientations of protein side chains Q72, N31 and R142, although these residues have previously been determined as important for binding to xylose oligomers by mediating polar contacts. The loss of these polar contacts is compensated for in binding to XXXG by polar interactions mediated by other protein residues, T74, R115 and Y149, which interact mainly with the branching xyloses of the xyloglucan oligomer. Taken together, the present study illustrates in structural detail how CH-π interactions can influence binding specificity and that flexibility is a key feature for the multi-specificity displayed by X-2 L110F, allowing for the accommodation of branched ligands. © Proteins 2014;. © 2014 Wiley Periodicals, Inc.
    Proteins Structure Function and Bioinformatics 10/2014; · 3.34 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: New tetra-iron(III) (K4[1]·25H2O·(CH3)2CO and K3[2]·3H2O·(OH)) and di-copper(II) (Na3[3]·5H2O) complexes as carbohydrate binding models have been synthesized and fully characterized used several techniques including single crystal X-ray crystallography. Whereas K4[1]·25H2O·(CH3)2CO and Na3[3]·5H2O are completely water-soluble, K3[2]·3H2O·(OH) is less soluble in all common solvents including water. The binding of substrates, such as d-mannose, d-glucose, d-xylose, and xylitol with the water-soluble complexes in different reaction conditions were investigated. In aqueous alkaline media, complexes K4[1]·25H2O·(CH3)2CO and Na3[3]·5H2O showed coordination ability toward the applied substrates. Even in the presence of stoichiometric excess of the substrates, the complexes form only 1:1 (complex/substrate) molar ratio species in solution. Apparent binding constants, pKapp, values between the complexes and the substrates were determined and specific mode of substrate binding is proposed. The pKapp values showed that d-mannose coordinates strongest to K4[1]·25H2O·(CH3)2CO and Na3[3]·5H2O. Syntheses, characterizations and detailed substrate binding study using spectroscopic techniques and single crystal X-ray diffraction are reported.
    Inorganic Chemistry 10/2014; · 4.79 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Protein-ligand docking is an essential technique in computer-aided drug design. While generally available docking programs work well for most drug classes, carbohydrates and carbohydrate-like compounds are often problematic for docking. We discuss the peculiarities of protein-carbohydrate interactions and their impact on protein-carbohy-drate docking and review the state of the art in docking of carbohy-drates to proteins. Finally, we give an overview of carbohydrate dock-ing studies and present a new docking method specifically designed to handle docking of carbohydrate-like compounds. BALLDock/SLICK combines an evolutionary docking algorithm for flexible ligands and flexible receptor side chains with carbohydrate-specific scoring and energy functions. The scoring function has been designed to identify accurate ligand poses, while the energy function yields accurate esti-mates of the binding free energies of these poses. On a test set of known protein-sugar complexes we demonstrate the ability of the ap-proach to generate correct poses for almost all of the structures and achieve very low mean errors for the predicted binding free energies.

Full-text (2 Sources)

Available from
May 28, 2014