合成带有新型三唑 STn 类似物的 MUC1 衍生糖肽。

Synthesis of MUC1-derived glycopeptide bearing a novel triazole STn analog.

机构信息

School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Av. Do Café S/n, Monte Alegre, 14040-903, Ribeirão Preto, SP, Brazil.

School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Av. Do Café S/n, Monte Alegre, 14040-903, Ribeirão Preto, SP, Brazil; Barão de Mauá University Centre, 423 Ramos de Azevedo Street, Jardim Paulista, 14090-180, Ribeirão Preto, SP, Brazil.

出版信息

Carbohydr Res. 2020 Dec;498:108155. doi: 10.1016/j.carres.2020.108155. Epub 2020 Sep 25.

DOI:10.1016/j.carres.2020.108155

PMID:33010570

Abstract

The synthesis of MUC1 glycopeptides bearing modified tumor-associated carbohydrate antigens (TACAs) represents an effective strategy to develop potential antitumor vaccines that trigger strong immune response. In this context, we present herein the multistep synthesis of the triazole glycosyl amino acid Neu5Ac-α/β2-triazole-6-βGalNAc-ThrOH 1 as STn antigen analog, along with its assembly on the corresponding MUC1 peptide to give NAcProAsp [Neu5Acα/β2-triazole-6-βGalNAc]ThrArgProGlyOH 2. Despite interacting differently with SM3 monoclonal antibody, as shown by molecular dynamic simulations, this unnatural triazole glycopeptide may represent a promising candidate for cancer immunotherapy.

摘要

合成带有修饰的肿瘤相关碳水化合物抗原（TACA）的 MUC1 糖肽是开发潜在抗肿瘤疫苗的有效策略，这种疫苗能引发强烈的免疫反应。在这种情况下，我们在此介绍了三唑糖基氨基酸 Neu5Ac-α/β2-三唑-6-βGalNAc-ThrOH1（作为 STn 抗原类似物）的多步合成，以及其在相应的 MUC1 肽上的组装，得到 NAcProAsp[Neu5Acα/β2-三唑-6-βGalNAc]ThrArgProGlyOH2。尽管如分子动力学模拟所示，与 SM3 单克隆抗体的相互作用方式不同，但这种非天然三唑糖肽可能是癌症免疫治疗的有前途的候选物。