1 research outputs found
Stabilization of Branched Oligosaccharides: Lewis<sup>x</sup> Benefits from a Nonconventional CāHĀ·Ā·Ā·O Hydrogen Bond
Although
animal lectins usually show a high degree of specificity
for glycan structures, their single-site binding affinities are typically
weak, a drawback which is often compensated in biological systems
by an oligovalent presentation of carbohydrate epitopes. For the design
of monovalent glycomimetics, structural information regarding solution
and bound conformation of the carbohydrate lead represents a valuable
starting point. In this paper, we focus on the conformation of the
trisaccharide Le<sup>x</sup> (GalĀ[FucĪ±(1ā3)]ĀĪ²(1ā4)ĀGlc<i>N</i>Ac). Mainly because of the unfavorable tumbling regime,
the elucidation of the solution conformation of Le<sup>x</sup> by
NMR has only been partially successful so far. Le<sup>x</sup> was
therefore attached to a <sup>13</sup>C,<sup>15</sup>N-labeled protein. <sup>13</sup>C,<sup>15</sup>N-filtered NOESY NMR techniques at ultrahigh
field allowed increasing the maximal NOE enhancement, resulting in
a high number of distance restraints per glycosidic bond and, consequently,
a well-defined structure. In addition to the known contributors to
the conformational restriction of the Le<sup>x</sup> structure (exoanomeric
effect, steric compression induced by the <i>N</i>HAc group
adjacent to the linking position of l-fucose, and the hydrophobic
interaction of l-fucose with the Ī²-face of d-galactose), a nonconventional CāHĀ·Ā·Ā·O hydrogen
bond between HāC(5) of l-fucose and O(5) of d-galactose was identified. According to quantum mechanical calculations,
this CāHĀ·Ā·Ā·O hydrogen bond is the most prominent
factor in stabilization, contributing 40% of the total stabilization
energy. We therefore propose that the nonconventional hydrogen bond
contributing to a reduction of the conformational flexibility of the
Le<sup>x</sup> core represents a novel element of the glycocode. Its
relevance to the stabilization of related branched oligosaccharides
is currently being studied