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带有四个Tn抗原糖模拟物单元和P3CS免疫佐剂的杯[4]芳烃:合成、表征及抗癌免疫学评价

Calix[4]arene decorated with four Tn antigen glycomimetic units and P3CS immunoadjuvant: synthesis, characterization, and anticancer immunological evaluation.

作者信息

Geraci Corrada, Consoli Grazia M L, Galante Eva, Bousquet Ennio, Pappalardo Maria, Spadaro Angelo

机构信息

Istituto di Chimica Biomolecolare, CNR, Via del Santuario 110, I-95028 Valverde (CT), Italy.

出版信息

Bioconjug Chem. 2008 Mar;19(3):751-8. doi: 10.1021/bc700411w. Epub 2008 Feb 23.

Abstract

A novel anticancer vaccine candidate built on a nonpeptidic scaffold has been synthesized. Four S-Tn tumor-associated glycomimetic antigens have been clustered onto a calix[4]arene scaffold bearing an immunoadjuvant moiety (P3CS). The immunogenicity of the synthetic construct has been investigated by immunization of mice in vivo. ELISA assay has evidenced that the tetravalent construct stimulates a higher production of anti-Tn antigen IgG antibodies when compared to an analogous monovalent compound. This result is ascribable to an antigen cluster effect and makes the reported vaccine candidate a good mimic of the natural motifs present on the mucine surface.

摘要

一种基于非肽支架构建的新型抗癌疫苗候选物已被合成。四种S-Tn肿瘤相关糖模拟抗原已聚集在带有免疫佐剂部分(P3CS)的杯[4]芳烃支架上。通过在体内免疫小鼠研究了合成构建体的免疫原性。ELISA分析表明,与类似的单价化合物相比,四价构建体刺激产生更高水平的抗Tn抗原IgG抗体。该结果归因于抗原簇效应,使得所报道的疫苗候选物很好地模拟了粘蛋白表面存在的天然基序。

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