The importance of orientation of exocyclic groups in a naphthoxyloside: A specific rotation calculation study

Abstract

2-Naphthyl β-D-xylopyranoside (XylNap) inhibits β-1,4-galactosyltransferase 7 (β4GalT7) and thereby growth of tumor cells both in vitro and in vivo. The binding pocket of β4GalT7 has a defined orientation of hydrogen bond acceptors and hydrophobic moiety. Knowing the orientation of the hydroxyl and naphthyl groups of this molecule would help in the development of more efficient inhibitors. In this work, we have tried, for the first time, to determine the exocyclic hydroxyl and aglycon groups orientation of XylNap, using ab initio descriptions, and calculation of the specific rotation values, in methanol solutions, using 2 different solvent descriptions: a dielectric continuum approach (polarizable continuum model [PCM]) and a microsolvated + continuum approach (MS + PCM). In the PCM approach, [α] D = −59 deg/(dm(g/cm 3 )) whereas for the MS + PCM approach [α] D = −29 deg/(dm(g/cm 3 )). The latter is in excellent agreement with the experimentally determined value in methanol solution, viz, [α] D = −30 deg/(dm(g/cm 3 )). This agreement allows us to say that the hydroxyl groups have similar orientations in xylose and XylNap, and the naphthyl group has a very well-defined ψ dihedral angle value in the most abundant conformations.

Polarimetry as a method for studying the structure of aqueous carbohydrate solutions: correlation with other methods

“…redistribution of solvent molecules around solute molecules (microsolvation, MS). These data indicate the promise of using polarimetry to study the microenvironment [37,38] of solute molecules in solutions with different structures, as well as for detecting rearrangements of supramers in solutions. An experimental study of the structure of aqueous solutions of levoglucosan using polarimetry began with freshly prepared solutions.…”

“…1b). The solvent was taken into account both within the polarizable continuum model (PCM) and by adding explicit water molecules (MS + PCM) [37]. For example, the calculated (PCM .…”

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“…1b). The solvent was taken into account both within the polarizable continuum model (PCM) and by adding explicit water molecules (MS + PCM) [37]. For example, the calculated (PCM (H 2 O)/B3LYP/6-311++G(2d,2p)//B3LYP/6-31+G(d,p)) specific optical rotation value for the GGG conformer is -5.46 deg•dm -1 deg•dm -1 •cm 3 •g -1 ).…”