284
Carbohydrate Antigens
classifed as simple heteropolysaccharides
and complex heteropolysaccharides. In the
Former, each polysaccharide chain is a ho-
mopolysaccharide, though two or more
diFFerent homopolymers are present in a
large heteropolysaccharide. In a complex
heteropolysaccharide, the polymer con-
tains two or more diFFerent types oF sugar
residues in a single branch.
2.2
Conformational Diversity
ConFormational flexibility is an intrinsic
property oF carbohydrate molecules. An
oligosaccharide in solution may exist in
many diFFerent conFormations with the
lower energy Forms predominating. Sig-
nifcant influence oF the composition oF
glycosidic linkages on the structural char-
acteristics oF oligosaccharides and polysac-
charides had been suggested For some
time. In the 1960s, it was pointed out: ‘‘It is
important to remember that each glucose
residue is Free to rotate around the
α
(1
6)
glycosidic bond so that the schematic rep-
resen
ta
t
ionin±
ig
.3Forisoma
l
toseisno
t
rigid. It may well be that the molecules
preFer certain conFormations in solution,
conFormations in which the planes oF the
ring bear a defnite orientation to one an-
other (see: Kabat, E.A., Structural Concepts
in Immunology and Immunochemistry,
Second Edition, Holt, Rinehart and Win-
ston, New York, 1976, Page 21).’’ In react-
ing with protein binding sites, however,
certain conFormations oF an oligosaccha-
ride may be selected and stabilized. Such
phenomenon was later termed
induced ft
.
Recent
technological
advances
have
made it possible to ‘‘see’’ whether an in-
duced ft indeed occurs when an oligosac-
charide intereacts with its receptor. This
can be achieved by comparing the solu-
tion conFormers oF oligosaccharides with
those in carbohydrate–protein complexes.
Nuclear magnetic resonance (NMR), flu-
orescence energy transFer (±ET), optical
rotation (OR), or Raman optical activity,
can be applied For detecting the molecular
flexibility in solution. X-ray crystallogra-
phy gives high-resolution determinations
oF molecular coordinates in the ‘‘Frozen’’
state. These comparative studies demon-
strated that (1)
α
(1
6) glycosidic bond in
an oligosaccharide is more flexible than
other linkages; (2) the linkages attaching
terminal residues to main chain struc-
tures are more flexible; (3) those in internal
chains are relatively stable; and (4) sugar
rings are generally rigid in conFormation,
but, induced ring distortion can be seen.
The
α
(1
6) glycosidic bond is superior
to other glycosidic bonds in conForma-
tional flexibility since three torsion angles
are required to defne the conFormation oF
this glycosidic bond (±ig. 4). Using NMR,
the solution conFormation oF melibiose
[Gal
α
(1
6)Glc] was compared with that
in its complex with ricin B-chain. The
disaccharide exists predominantly as two
conFormers, resulting From rotation about
the
α
(1
6)linkage. Only one oF the two
conFormers binds to the lectin. Enzymes
may also recognize only certain conForma-
tions oF their carbohydrate substrates. Glc-
NAc transFerase V can use Man
α
(1
6)
Man For extending N-linked oligosaccha-
rides into higher branched structures. To
see which conFormer is suitable For the
enzyme, two rigid bicyclic analogs oF Man
α
(1
6) Man were generated by fxing the
α
(1
6)linkage in either a gauche–gauche
(gg) or gauche–trans (gt) conFormation. It
was shown that only the gg conFormer
was used as substrate by the enzyme.
Thus, this enzymatic selectivity depends
on the conFormational property oF carbo-
hydrate molecules.
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