Environmental Engineering Reference
In-Depth Information
OR
Fig. 1 Disaccharide
repeating units of heparan
sulfate and heparin. Sulfation
(R
6
6
4
O
5
HOOC
O
-SO 3 ) at Carbon 6
(known as 6 -O -sulfated
glucosamine, GlcN6S) of
glucosamine is common.
Sulfation (R =
=
1
O
4
5
HO
2
O
3
O
HO
2
1
NHR''
3
OR'
-SO 3 )at
Carbon-2 of iduronic acid
(known as 2- O -sulfated
iduronic acid, IdoUA2S) is
common. Sulfation at
Carbon-3 of glucosamine
(known as 3- O -sulfated
glucosamine, GlcN3S) is rare.
Both N -acetylated
(R =
Glucosamine
(GlcN)
Glucuronic acid
(GlcUA)
OR
6
6
HOOC
4
O
5
4
O
5
1
OH
HO
O
2
3
acetyl, GlcNAc) and
N -sulfated (R =
3
NHR''
O
O
-SO 3 ,
GlcNS) are common.
N -unsubstituted glucosamine
(R = -H, GlcNH 2 )isalow
abundant component. IdoUA
(2S) is presented in both 1 C 4
and 2 S 0 conformation. Both
conformations are presented
R'O
2
1
Iduronic acid
(IdoUA)
Glucosamine
(GlcN)
6
O
5
OH
6
- O 2 C
O
5
2
- O 2 C
O
1
4
1
4
O
OSO 3 -
3
HO
2
O
3
O
OSO 3 -
2 S 0
1 C 4
IdoUA(2S)
glucosamine is a rare component of HS and plays an important role in binding to
antithrombin (AT) [20] as well as binding to HSV-1 gD [29]. The distribution of
different sulfo groups determines the biological function of HS. The structures of
heparin and HS are similar; however, heparin has a higher content of IdoUA and
more sulfo groups per disaccharide unit [20]. In fact, heparin has the most negative
charge of all glycosaminoglycans.
2.2 Biosynthesis of HS
Heparin and HS share the same biosynthesis pathway. Understanding the biosyn-
thetic mechanism of HS provides a tool to alter the synthesis of HS in the cells,
and helps to delineate the contribution of HS in a specific biological process.
Consequently, the results can be employed to improve the pharmacological drug
properties of anticoagulant heparin and aid in the development of HS/heparin-based
therapeutic agents with anticancer and antiviral activities. It should be noted that
unlike proteins and nucleic acids, the synthesis of polysaccharides does not have
a template; the specific saccharide sequences are governed by the expression level
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