Biomimetic synthesis of the tumor-associated (2,3)-sialyl-T antigen and its incorporation into glycopeptide antigens from the mucins MUC1 and MUC4
Biomimetic synthesis of the tumor-associated (2,3)-sialyl-T antigen and its incorporation into glycopeptide antigens from the mucins MUC1 and MUC4
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DOI：
10.1002/chem.200400228
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发表时间：
2004-09-06
影响因子：
4.3
通讯作者：
Kunz, H
中科院分区：
文献类型：
--
作者：
Dziadek, S;Brocke, C;Kunz, H
上皮肿瘤细胞上的糖蛋白通常表现出异常的糖基化特征。由下调的葡糖胺转移和过早唾液酸化导致的聚糖侧链的不完全形成导致额外的肽表位，其在粘蛋白型糖蛋白中变得可接近免疫系统。这些癌症特异性结构改变被认为是对肿瘤细胞进行选择性免疫攻击的有希望的基础。在肿瘤相关糖抗原中，（2，3）-唾液酸-T抗原已被鉴定为最丰富的聚糖，在几种不同的癌细胞系中发现。根据线性仿生策略，通过受保护的半乳糖胺-苏氨酸前体的逐步聚糖链延伸来合成（2，3）-唾液酸-T抗原。为了构建结合肽和糖基序的免疫刺激抗原，通过连续固相合成将该抗原掺入来自粘蛋白MUC 1和MUC 4的糖肽部分结构中。
Glycoproteins on epithelial tumor cells often exhibit aberrant glycosylation profiles. The incomplete formation of the glycan side chains resulting from a down-regulated glucosamine transfer and a premature sialylation results in additional peptide epitopes, which become accessible to the immune system in mucin-type glycoproteins. These cancer-specific structure alterations are considered to be a promising basis for selective immunological attack on tumor cells. Among the tumor-associated saccharide antigens, the (2,3)-sialyl-T antigen has been identified as the most abundant glycan, found in several different carcinoma cell lines. According to a linear biomimetic strategy, the (2,3)-sialyl-T antigen was synthesized by a stepwise glycan chain extension of a protected galactosamine-threonine precursor. For the construction of immunostimulating antigens combining both peptide and saccharide motifs, this antigen was incorporated into glycopeptide partial structures from the mucins MUC1 and MUC4 by sequential solid-phase synthesis.