Environmental Engineering Reference
In-Depth Information
HOOC
OSO 3 -
O
O
OSO 3 -
O
HO
O
O
O
HO
O
OSO 3 -
HO
OSO 3 -
O
NHSO 3 -
HO
O
O
HOOC
OSO 3 -
OSO 3 -
O
HO
O
- O 3 SHN
O
O
HO
O
OSO 3 -
HOOC
HO
NHSO 3 -
HO
OH
HOOC
OSO 3 -
NHSO 3 -
3-OST-3
HOOC
OSO 3 -
O
O
OSO 3 -
O
HO
O
O
O
HO
OSO 3 -
O
HO
OSO 3 -
O
NHSO 3 -
HO
HOOC
OSO 3 -
O
O
OSO 3 -
O
HO
O
- O 3 SHN
- O 3 S O
O
O
O
HOOC
HO
OSO 3 -
NHSO 3 -
HO
OSO 3 -
OH
HOOC
3- O -sulf ated octasaccharide
NHSO 3 -
Fig. 8 Preparation of 3- O -sulfated octasaccharide that inhibits the entry of HSV-1. The substrate
was purified from partially depolymerized heparin with heparin lyases. 3-OST-3 was utilized to
transfer a sulfo group to the substrate to synthesize 3- O -sulfated octasaccharide
octasaccharide was indeed an inhibitor for HSV-1 infection. The structure of
octasaccharide was characterized by ESI-MS and non-reducing and reducing end
sequence analysis. The structure has been determined to be
UA2S-GlcNS6S-
IdoUA2S-GlcNS6S-IdoUA2S-GlcNS6S3S-IdoUA2S-GlcNS6S (
-
L-threo-hex-enopyranosyluronic acid). These results demonstrate the application
of enzymatic synthesis for a structurally defined HS oligosaccharide to inhibit
HSV-1infection.
UA is deoxy-
α
4.6 De Novo Synthesis of Heparin/HS Backbone
A major drawback of heparin/HS enzymatic synthesis from heparosan is that the
heparosan is not a pure substrate because the size of the individual polysaccharide
chain is not defined. Efforts have been made to synthesize size-defined HS back-
bones. One method is to use heparin lyase digested heparosan. Indeed, Rosenberg's
lab has used this method to synthesize an AT-binding pentasaccharide. However,
controlling the extent of digestion is difficult and HS oligosaccharides of other size
and structures are difficult to achieve in large quantities. In contrast, De novo syn-
thesis using HS backbone synthases provides a promising alternative approach.
Bacterial glycosyl transferases offer the hope for the synthesis of HS oligosac-
charide backbone. It's known that some bacteria such as E. coli K5 strain and
Pasteurella multocida ( P. multocida ) can produce heparosan. Therefore, one can
take advantage of the synthases involved in the biosynthesis of heparosan for HS
backbone synthesis. Our lab and DeAngelis' lab have characterized some synthases
involved in the biosynthesis of heparosan [48-51]. In E. coli , KfiA was originally
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