Biomedical Engineering Reference
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OH
OH
COOH
OH
OH
HO
O
O
COOH
O
AcHN
HO
AcHN
OH
O
OH
OH
HO
OH
OH
O
HO
CH
COOH
O
HO
HO
OH
CHO
O
HO
O
HO
HO
O
OH
OH
O
OH
OH
AcHN
Reductive amination
with NaBH
3
CN
OH
OH
OH
HO
O
HO
6SL-chitosan
O
OH
HO
O
OH
OH
6SL
OH
OH
O
O
O
O
OH
OH
NH
2
NH
2
n
Chitosan
Figure 2.23
Synthesis of 6SL-chitosan.
N
-succinyl-sialic acid-bound chitosan. Water-soluble α-galactosyl chitosan prepared by
the same strategy as sialic acid showed specific binding against a galactosyl-specific lectin
(
Griffonia simplicifolia
) [210]. Different types of spacers have been prepared on sialic acid or
α-galactosyl epitope-bound chitosans [211]. These epitope-bound chitosans may be useful
as potent inhibitors of influenza viruses or blocking agents for acute rejection [210,212].
Umemura et al. [213] modified chitosan with multiple sialyl saccharides, α-2,6-sialyllactose
or free sialyl glycan, using reductive amination reaction. After only one step of the proce-
dure, the binding inhibitor of influenza virus, 6SL-chitosan, was obtained that has multi-
ple Neu5Acα2, 6Gal components recognized by the viral hemagglutinin (Figure 2.23). It
might be difficult to add 6SL to chitosan with a DS of more than 40% owing to the chitosan
structure. It is interesting that the DS values of 6SL-chitosan were in inverted order of the
amount of 6SL in the reaction solution. It is considered that the 0.5 equivalent of 6SL was
sufficient for this synthesis, and excessive amounts of 6SL might have caused too crowded
a condition for the reductive amination of chitosan glucosamine.
To compare with the inhibitory activity of 6SL-chitosan, another binding inhibitor, FSG-
chitosan, by substituting FSG for 6SL (
Figure 2.24),
was synthesized. Free sialyl glycan
(FSG) is a biantennary decasaccharide that contains two sialic acids at each nonreducing
terminal. The highest DS value reached only 4.4% with the resulting compound. The
resulting inhibitors showed sufficient inhibitory activity against influenza virus infection
in MDCK cells compared to that of α-2, 6-sialyllactose, or free sialyl glycan.
2.10 CD-Linked Chitosan
CDs are cyclic oligosaccharides built from six to eight (α = 6, β = 7, γ = 8) d-glucose units
and are formed during the enzymatic degradation of starch and related compounds. CD
has the merit of a hydrophobic cavity, which is easy to assemble with other molecules.
Chitosan has the merit of degradation slowly in an organism. Therefore, grafting CD mol-
ecules into chitosan-reactive sites may lead to a molecular carrier that possesses the cumu-
lative effects of inclusion, size specificity, and transport properties of CDs as well as the
controlled release ability of the polymeric matrix [214]. The products obtained by CD
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