Biomedical Engineering Reference
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OH
OH
OH
O
O
O
O
O
O
HO
HO
HO
NHAc
R
′
HN
NR
′
0.2
x
0.8-
x
O
OH
HO
OH
O
NHAc
COONa
HO
O
AcHN
O
O
OH
O
HO
HO
O
OH
NaOOC
NR
N
RN
N
N
OH
COONa
HO
RN
R
N
N
N
OH
O
O
O
HO
NHAc
O
AcHN
NaOOC
OH
N
R
NR
OH
OH
NaOOC
HO
RN
O
NR
HO
O
HO
O
OH
HO
OH
O
AcHN
NaOOC
NHAc
NaOOC
O
O
HO
NaOOC
O
OH
OH
O
HO
HO
HO
OH
HO
NHAc
HO
NHAc
HO
OH
Figure 2.46
Chemical structure of chitosan-sialodendrimer hybrid.
In another convergent approach taken by the team of Sashiwa et al. [318-320], first tetra-
ethylene glycol was modified in five or seven steps to synthesize the scaffold of dendrimer.
PAMAM dendrimers of generation (
G
) from 1 to 3 bearing tetraethylene glycol spacer were
prepared, attached to sialic acid by reductive
N
-alkylation, and finally attached to chitosan
(Figure 2.46). The DS of dendrimer decreased with increasing generation as 0.08 (G1), 0.04
(G2), and 0.02 (G3) owing to the steric hindrance of dendrimer.
A chitosan-dendrimer hybrid prepared by method B is shown in
Figure 2.47
[321]. As
the construction of the hybrid was difficult from the original chitosan, a derivative,
N
-methoxycarbonylethylchitosan (NMCC), was used as the chitosan backbone. PAMAM
dendrimers (
G
= 1-5) having a 1,4-diaminobutane core were attached to NMCC by amida-
tion under conditions that prevented cross-linking. The hybrids could be prepared even at
high generations (
G
= 4 or 5), although the DS of dendrimer was decreased with increasing
generation of dendrimer from 0.53 (
G
= 1) to 0.17 (
G
= 4) or 0.11 (
G
= 5). Because this hybrid
was soluble in acidic solutions, undesired cross-linking did not occur. However, two or
more intermolecular binding points were observed. Finally, sialic acid was successfully
attached to the primary amine of the dendrimer with DS ranging from 0.7 to 1.4 per glu-
cosamine unit, which indicates a highly convergent synthesis of sialic acid in the chitosan
backbone. Given the fact that flu virus hemagglutinins exist as clusters of trimers (200-
300/virions), it is likely that the novel dendronized chitosan-sialic acid hybrids prepared
by method B will present added beneficial architectures not present in previously reported
sialodendrimers [322,323].
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