Synthetic and immunological studies of N-acyl modified S-linked STn derivatives as anticancer vaccine candidates
Synthetic and immunological studies of N-acyl modified S-linked STn derivatives as anticancer vaccine candidates
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N-酰基修饰的 S-连接 STn 衍生物作为抗癌疫苗候选物的合成和免疫学研究
DOI：
10.1039/c4ob02424a
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发表时间：
2015-01-01
影响因子：
3.2
通讯作者：
Ye, Xin-Shan
中科院分区：
文献类型：
--
作者：
Huo, Chang-Xin;Zheng, Xiu-Jing;Ye, Xin-Shan
众所周知，肿瘤细胞表达一些异常聚糖，称为肿瘤相关碳水化合物抗原（TACA）。TACA是开发基于碳水化合物的抗癌疫苗的良好靶标。然而，主要问题之一是碳水化合物抗原具有弱免疫原性。为了解决这个问题，设计并制备了许多非天然的N-修饰的S-连接的STn类似物。修饰后的STn二糖与双功能己二酸对硝基苯基二酯反应生成相应的活化酯，再与匙孔血蓝蛋白（KLH）偶联，得到相应的蛋白偶联物。在小鼠模型中评价这些糖缀合物的免疫学性质。结果表明，修饰的糖缀合物刺激了能够识别天然存在的STn抗原的IgG抗体的产生，有助于发现基于碳水化合物的抗癌疫苗候选物。
It is well known that tumor cells express some aberrant glycans, termed tumor-associated carbohydrate antigens (TACAs). TACAs are good targets for the development of carbohydrate-based anticancer vaccines. However, one of the major problems is that carbohydrate antigens possess a weak immunogenicity. To tackle this problem, a number of unnatural N-modified S-linked STn analogues were designed and prepared. Reaction of the modified STn disaccharides with bifunctional adipic acid p-nitrophenyl diester provided the corresponding activated esters, which was followed by the conjugation with keyhole limpet hemocyanin (KLH), affording the corresponding protein conjugates. The immunological properties of these glycoconjugates were evaluated in a mouse model. The results showed that the modified glycoconjugates stimulated the production of IgG antibodies that are capable of recognizing the naturally occurring STn antigen, helping the discovery of carbohydrate-based anticancer vaccine candidates.