2056
C. Brocke, H. Kunz
LETTER
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of two steps). It is characteristic for the steric hindrance at
position 4 of the galactose within the saccharide that the
OH group in this position remained unacetylated during
the numerous capping steps. After hydrogenolysis of the
sialic benzyl esters of 20 (not applicable to non-sialylated
glycopeptides) and removal of the O-acetyl groups by
transesterification with catalytic NaOMe in methanol at
pH 9, the pure [(2,6)-sialyl-T]2-MUC4 glycopeptide 21
was isolated in an overall yield of 20% (based on the load-
ed resin 9). Table 1 gives an overview of the results of the
other MUC4 glycopeptides synthesized by this
methodology. For comparison, the acetylated non-
glycosylated MUC4 tandem repeat peptide sequence 1
was prepared.
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The results given in Table 1 show that all MUC4 tandem
repeat glycopeptides containing one (22–26) or two (21,
27–29) tumour-associated carbohydrate antigens are
accessible by the described method. An advantage is the
hydrogenolytic cleavage of the sialic benzyl ester
avoiding exposition of the glycopeptides 21 and 29 to
stronger basic conditions. This is important as the
glycosylated Thr-10 has a carboxamide function that can-
not be deprotonated. The treatment of (2,3)-sialyl-T
MUC4 glycopeptide 26 with aqueous NaOH necessary
for the removal of all O-acetyl groups shows that the
glycopeptides also withstand these conditions. The
economical method by which all carbohydrate antigen
amino acid conjugates are accessible from the TN
threonine building block 2 is the basis of the described
syntheses. The obtained set of MUC4 glycopeptide anti-
gens is presently evaluated in systematic immunological
studies in terms of their effects on peripheral blood
lymphocytes9a and their conformational properties in
aqueous solution.9b
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Synlett 2003, No. 13, 2052–2056 © Thieme Stuttgart · New York