Chemistry Reference
In-Depth Information
inhibitor.
107
Multisulphated fucooligosaccharides (DP 2 to 6 and up to 5
sulphate groups per molecule) were prepared by Anastyuk et al.by
autohydrolysis of a fucoidan.
108
The mixture slightly inhibited cell pro-
liferation and colony formation of melanoma cell lines. The authors
thought that the inhibition activity of fucoidans depended on the pres-
ence of both sulphates and (1
4)-linked a-
L
-Fucp residues in the main
chain. k-Carrageenan oligosaccharides (MW
-
1 kDa) were prepared
by Song et al.
109
and modified by sulphation (48 % w/w), acetylation
(acetylation degree 1.1) or phosphorylation (3 % w/w). The authors
underlined the important role of sulphate groups as they enhanced their
antitumor effect and boosted antitumor immunity. The more sulphated
l-carrageenan oligosaccharides (DP 4 to 12) obtained by acidic hydrolysis
by Yan et al.
110
showed to have antiangiogenic activities at low concen-
tration but cytotoxic properties at high concentration (W800 mg/ml) by
elicitation of reactive oxygen species production. Ferro, Hammond,
Dredge et al.
58b,111
studied the biological properties of malto- or manno-
oligosaccharide mimetics of HS or PI-88 coupled to lipophilic groups
(like in PG545 a polysulphated cholestanylmaltotetraoside). The com-
pounds showed to be inhibitors of heparanase and HS-binding but also
of angiogenic growth factors, and thus displayed improved antitumor
and antimetastatic activities. Oligogalacturonan showed also anti-
angiogenic activity depending of the DP. A too high DP or a too low DP
lead to no activity. Ding et al.
112
have found that an oligogalacturonan
fraction (DP 5 to 10) demonstrated the strongest inhibition effect on cell
tube formation. HA oligosaccharides (DP 2 to 40) are involved in
angiogenesis and may lead to cell proliferation; they exhibit biological
functions that are quite distinct from those of the native HA which tends
to inhibit angiogenesis. Wang et al. prepared HA oligosaccharides (DP 4,
6, 8 and 10) from HA using hyaluronidase, and compared their angio-
genic activities.
113
DP 6, 8 and 10 showed high activities. Differences of
biological effects between a native HA polymer and the oligosaccharides
have been already observed on cluster determinant 44 (CD44, a major cell
surface receptor for HA) binding. Gao et al.
114
showed that HA oligo-
saccharides could attenuate the stimulation of cell surface CD44
clustering caused by HA polymer. Hepatocyte growth factor (HGF) is an
in vivo potent angiogenic factor which induces endothelial cells to
proliferate and migrate. Poly- and oligosaccharides like heparin and de-
rivatives may stimulate production of HGF at the level of RNA translation.
Nakamura et al. studied the production of HGF in presence of fucoidan
derived oligosaccharides.
115
Fucoidan derived oligosaccharides (DP 6
and higher) stimulate the production of HGF. Heparin/HS and DS
interact both with high anity with HGF/scatter factor (SF) and act as
co-factors for the activation of the tyrosine kinase receptor MET while CS
not. The activation of MET is required for biological processes such as
organ regeneration. But, a dysregulation of HGF/SF can lead to tumour
growth invasion; inhibitors are then necessary. Lyon et al. studied the
binding properties of short oligosaccharides obtained by enzymatic
digestion from HS and DS to NK1 region of the N-domain of HGF/SF in
order
E
inhibitors.
116
to find small
GAG backbone and sulphate
Search WWH ::
Custom Search