Biomedical Engineering Reference
In-Depth Information
a stronger control of the glycosidic linkage, or at least to make the purification
steps easier. Among the first examples of this strategy [20-21], Kunz has
reported the synthesis of several extracellular peptide sequences from the tandem
repeat domains of the native epithelial mucin glycoproteins. The synthesis starts
from a galactosyl bromide which was coupled to the hydroxyl side chain of the
Fmoc-protected threonine residue that is readily usable in Fmoc solid phase
peptide synthesis [22]. Due to the presence of azide non-participating group at
carbon 2, the
ŋ
-glycosidic linkage was recovered in moderate yield. After
subsequent azide reduction and deacetylation, the Fmoc protected Tn building
block
1
was obtained (Figure 4).
OH
CO
2
H
HO
OH
O
O
AcHN
HO
HO
O
HO
AcHN
O
3
OtBu
OH
FmocNH
HO
2
O
OH
CO
2
H
O
S
HO
OH
HO
O
AcHN
S
AcHN
OEt
O
HO
OtBu
FmocNH
OH
CO
2
H
HO
OH
O
1
O
O
AcHN
HO
OH
H O
HO
O
O
O
HO
OH
AcHN
O
4
OtBu
FmocNH
O
Fig. 4. Synthesis of 2,6-sialyl Tn and 2,6-sialyl TF building blocks.
From this minimal key building block
1
, further extensions can be realized to
access more complex antigenic carbohydrates motifs. Taking advantage of the
difference in reactivity of hydroxyl functional groups, a regioselective sialylation
was performed on the galactosyl moiety with sialyl-xanthogenate
2
to afford
ŋ
2,6-sialyl-Tn
3
[22-23] which was converted successively into
Ҭŋ
2,6-sialyl-TF
antigen
4
[24]. The same group further developed an efficient synthesis of the
MUC-1 glycopeptide antigen
5
containing the immunodominant PDTRP motif
[23]. The incorporation of
3
into the sequence was performed on solid support
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