Gábor I. Csonka*
Department of Inorganic Chemistry, Budapest University of Technology, H-1521 Budapest
Carlos P. Sosa
Silicon Graphics Inc. 655 E. Lone Oak Dr. Eagan, MN 55123, USA
Imre G. Csizmadia
Department of Chemistry, University of Toronto, Toronto, Ontario, Canada M5S 3H6
Introduction
As carriers of information, oligosaccharides have far greater potential
than nucleic acids or proteins. Several types of hexapyranose units can
connect to each other to form oligosaccharides in different sequences
and different positions [1,1], [1,3], [1,4], [2,3] etc. The chain can be
branched or unbranched and the connection can be via - or glycosidic linkage.
Furthermore, the numerous OH groups can assume g+, a and gpositions.
t
g-
g+
Gg-
g+
t
O
axial
(Man) g+
gg-
t
g+
O
O
T
4
2
3
t
g-
g+
O
t
6
t
gg- G+
O
g- 5
1
equatorial
t (Glc)
g+
O
g+
t
g+
equatorial ()
axial ()
g+
O
t
gFigure 1. Illustration of the conformational space of the C1 piranose ring of the (,)-D-glucose and mannose (OH axial at
C2). The T, G+ and G- symbols denote the oxygen of the possible rotamers of CH2OH group, the lower case letters show the
possible rotamers of OH hydrogens.
4
Such tremendous structural variation can code a great deal of
information. This is why carbohydrates play a vital role in the process of
cell recognition. An example of cell recognition may be seen in the case
of sialyl Lewisx (sLex, NeuAc--2,3-Gal--1,4-[Fuc--1,3]-GlcNAc)
with its antigen properties. This tetrasaccharide is displayed on the
terminus of glycolipids that are present on the surface of human white
blood cells.
Figure Overlap between the experimental X-ray and ab initio HF/6-31G(d) (pink) structure
Figure Overlap between the two experimental X-ray structures
Oligosaccharides are frequently attached to proteins via Nglycosidic (A) or O-glycosidic (B) linkage.
H
O
N
CH
C
CH2
H OH
H
C
O
HO
NH
HO
H
NHAc
H

OH OH
O
H
H
H
HO
H
H
A
O
H
NHAc

O
CH2
B
N
H
CH
C
O
The carbohydrate antennas of glycopetides are involved in molecular
recognition processes the hydrogen bonds are reorganized.
Carbohydrate recognition in the nature
1. Enzymes bind and transform carbohydrates
2. Antibodies over 70% directed towards oligosaccharide epitopes
3. Lectins recognition of cell-surface oligosaccharides, adhesion (in animals,
plants, bacteria and viruses)
4. Bacterial periplasmic proteins –high binding constants to monosaccharides
Lectins
1. bacterial and viral lectins initiate the infection of the target cells (e.g.
influenza haemagglutinin)
2. collectins (e.g. mannose binding protein) as part of an antibodyindependent immune response
3. selectins mediate the recruitment of leukocytes into inflammatory tissue
sites
Carbohydrates in their pyranose and furanose forms are characterized by an
array of polar functional groups. Most are OH groups – donation and
acceptance of hydrogen bonds
Carbohydrate recognition: surround these groups with complementary H-bonds
donor or acceptor functionality. – Example: glucose in intermolecular
complex.
Experimental techniques
Crystal structures
 packing forces distort the hydrogen bonds (and H positions are uncertain)
 provide precise test possibilities for force fields applied for solid-phase
 CSDB 55 structures of un-substituted di-, 17 tri-, 4 tetrasaccharides (out
of 160k)
 PDB – cocrystallization of lectins with oligosaccharides (less rigid
structure!)
NMR structures
 in solution (no intramolecular H-bonds)
 imprecisions, averaging effects, NOE results
 complex structures
Calorimetric studies
 complexation enthalpy
 complexation entropy
K
Computational Chemistry
The correct description of the conformational space of oligosaccharides
is a challenging problem for the computational chemistry.
Carbohydrates are rather difficult tests for MM methods because they
have densely packed highly polar functional groups and the
conformational energies depend on stereoelectronic effects.
Thus we performed ab initio HF, MP2, CCSD(T) and DFT analysis of
the hydrogen bonding between adjacent OH groups





in 1,2-ethanediol,1,2.
in a 6-deoxy hexose: L-fucose.3,4
D-glucose5,6 as well as D-mannose.
Lewisx trisaccharide (Lex, Gal--1,4-[Fuc--1,3]-GlcNAc) and its analogs.7,8
O-Glycosides of serinediamide, to be published (see figures)
Methodology
 Finding the elements of the conformational space: MM + Monte Carlo or
dynamics – problems with force fields, the MM relative energies are
usually not reliable.
 Ab initio HF/6-31G(d) for more reliable energetic results for the elements
of the conformational space (especially good energetics for
monosaccharides)
 DFT and MP2 studies, for correlation effects
 Basis set convergence studies
 Zero point vibration and thermal corrections  H
The most stable rotamers of the computed ab initio conformational
space are published on the WWW: http://web.inc.bme.hu/csonka/
Acknowledgements
G.I.C. is thankful for the support from Professor Lecomte for the Gordon Conference. G.I:C. also thanks the
support of Ministry of Education (MEC-00841/2001). The work was partly supported by an OTKA Grant (T
034764, Hungary).
References
1
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3
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4
G.I. Csonka, K. Éliás, I. Kolossváry, C.P. Sosa, and I.G. Csizmadia, J. Phys. Chem. A 1998, 102, 1219.
5
G.I. Csonka, K. Éliás and I.G. Csizmadia, Chem. Phys. Letters, 1996, 257, 49.
6
G.I. Csonka, I. Kolossváry, P.Császar, K. Éliás and I.G. Csizmadia, J.Mol. Struct. (THEOCHEM), 1997,
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7
G.I. Csonka, C.P. Sosa, and I.G. Csizmadia, J.Phys. Chem. A 2000, 3381, 104.
8
G.I. Csonka, and C.P. Sosa J.Phys. Chem. A 2000, 7113, 104.
2