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用于开发肿瘤选择性疫苗的合成糖肽。

Synthetic glycopeptides for the development of tumour-selective vaccines.

作者信息

Kunz Horst

机构信息

Institut fuer Organische Chemie, Johannes Gutenberg-Universitaet Mainz, D-55099 Mainz, Germany.

出版信息

J Pept Sci. 2003 Sep;9(9):563-73. doi: 10.1002/psc.477.

Abstract

Based on structural information reported for the tumour-associated epithelial mucin MUC1, glycopeptides have been synthesized which contain tumour-associated saccharide antigens. such as the Thomsen-Friedenreich (T), TN or sialyl TN antigen. in combination with peptide sequences of the tandem repeat region of MUC1. Solid-phase syntheses have been carried out using N-Fmoc protected O-glycosyl serine and threonine building blocks and an allylic anchor which is stable to basic and acidic conditions, but can be cleaved under neutral conditions in a palladium(0)-catalysed allyl transfer reaction. In addition. a (2-3)sialyl T antigen threonine building block was prepared by a chemoenzymatic strategy and used in the synthesis of an N-terminal glycopeptide antigen of leukosialin (CD43). The proliferation of cytotoxic T cells could be induced using a construct consisting of a MUC1-glycopeptide antigen and a T cell epitope.

摘要

基于已报道的肿瘤相关上皮粘蛋白MUC1的结构信息,已合成了含有肿瘤相关糖抗原的糖肽,如桑福德-弗里德赖希(T)抗原、TN抗原或唾液酸化TN抗原,并结合了MUC1串联重复区域的肽序列。使用N-芴甲氧羰基(N-Fmoc)保护的O-糖基化丝氨酸和苏氨酸构建块以及在碱性和酸性条件下稳定但可在中性条件下通过钯(0)催化的烯丙基转移反应裂解的烯丙基锚进行了固相合成。此外,通过化学酶法策略制备了一种(2-3)唾液酸化T抗原苏氨酸构建块,并用于合成白细胞唾液酸蛋白(CD43)的N端糖肽抗原。使用由MUC1糖肽抗原和T细胞表位组成的构建体可诱导细胞毒性T细胞的增殖。

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