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tri-, penta- and heptasaccharides of the regular region of the poly-
saccharide.
67
Interaction of these oligosaccharides with eosinophil-
derived neurotoxin (EDN), a cationic ribonuclease and a mediator
produced by human eosinophils, was further investigated. The synthetic
heptasaccharide at 5mgmL
1
was responsible of the inhibition of EDN
binding to the bronchial epithelial cell surface while no inhibition has
been observed for the tri- and pentasaccharides at 10mgmL
1
. This can
lead to protection of bronchial epithelial cells from EDN induced damage
and thus from asthma. As viruses can initiate infection of cells by binding
to cell surface GAG, sulphated oligosaccharides and mimetics should
exhibit antiviral activities. k-Carrageenan oligosaccharides (MW 3 to
10 kDa) were prepared by Tang et al.
90
by acidic hydrolysis under
microwave heating and some of them were acetylated (acetylation degree
1.5) or acetylated and sulphated (acetylation degree 1.0, sulphation de-
gree 2.4). The anti-influenza virus activities of these oligo- k-carrageenans
were similar to ribavirin. Better activities were obtained for the sulphated
oligosaccharides. GAG or GAG-like receptors may promote respiratory
syncytial virus (RSV) infection of humans. GAG chains mimetics may
protect humans from RSV. Trybala et al.
120
studied the anti-RSV activity
of sulphated tetra- and pentasaccharides linked to lipophilic groups.
They demonstrated that the cholestanol-conjugated polysulphated mal-
totetrose (PG545) exhibited higher anti-RSV activity in cultured cells than
unmodified sulphated oligosaccharides. When sulphated pentasacharide
is substitued by a dodecyl chain, then the anti RSV activity is less
important than for the cholestanol substituted one. Furthermore, PG545
displayed virus inactivating (virucidal) activity, a feature absent in
sulphated oligosaccharides. Some of these oligosaccharides show anti
HIV-1 and anti HSV-2 activities when a cholestanyl or other hydrophobic
group such as an alkyl and aromatic group substitutes the sulphated
oligosaccharides.
121
They possibly interact with GP120 and with the
virion lipids thus blocking viral attachment to the cell surface through
binding to the virus. Hung et al.
64
studied the influence of sulphated
positions (even a O-3 of a O-6,N-sulphated glucosamine) and substitution
on two HS octasaccharides on the anti HSV-1 activity. The two octa-
saccharides showed anti HSV-1 activities independently of the sulphate
positions. A 3-O-sulphated heparin octasaccharide has been successfully
used against HSV-1 infection with higher anity than the one lacking the
3-O-sulphate. Infection can be blocked by saturating the HSV envelope
glycoprotein gD using the active octasaccharide.
122
4.4 Alzheimer disease
Alzheimer disease is characterized by the formation of amyloid plaques
composed by accumulated neurotoxic b-amyloid peptides. These peptides
are generated from amyloid precursor protein by proteolytic processing
implicating the protease b-secretase BACE-1. The proteolytic degradation
of the amyloid precursor protein can be modulated by inhibition of the
BACE-1. Boons et al.
61
synthesized well-defined HS oligosaccharides and
found that one tetrasaccharide was able to inhibit it well. Tyler et al.
123
synthesized a library of 16 HS hexa- to dodecasaccharides. Screening of
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