MUC1 is a membrane glycoprotein, which in adenocarninomas is overexpressed and exhibits truncated O‐glycosylation. Overexpression and altered glycosylation make MUC1 into a candidate for immunotherapy. Monoclonal antibodies directed against MUC1 frequently bind an immunodominant epitope that contains a single site for O‐glycosylation. Glycosylation with tumor carbohydrate antigens such as the Tn‐antigen (GalNAc‐O‐Ser/Thr) results in antibodies binding with higher affinity. One proposed model to explain the enhanced affinity of antibodies for the glycosylated antigen is that the addition of a carbohydrate alters the conformational properties, favoring a binding‐competent state. The conformational effects associated with Tn glycosylation of the MUC1 antigen was investigated using solution‐state NMR and molecular dynamics. NMR experiments revealed distinct substructures of the glycosylated MUC1 peptides compared with the unglycosylated peptide. Molecular dynamics simulations of the MUC1 glycopeptide and peptide revealed distinguishing differences in their conformational preferences.

中文翻译：

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糖基化对MUC1免疫显性表位构象集合的作用。

MUC1是一种膜糖蛋白，在腺癌中过表达并表现出截短的O-糖基化。过表达和糖基化改变使MUC1成为免疫疗法的候选药物。针对MUC1的单克隆抗体经常结合一个免疫优势表位，该表位包含一个O-糖基化位点。肿瘤糖类抗原（例如Tn抗原（GalNAc-O-Ser / Thr））的糖基化可导致抗体以更高的亲和力结合。一个提出的解释抗体对糖基化抗原亲和力增强的模型是，添加碳水化合物会改变构象特性，有利于具有结合能力的状态。使用溶液状态NMR和分子动力学研究了与MUC1抗原的Tn糖基化相关的构象效应。NMR实验显示，与未糖基化的肽相比，糖基化的MUC1肽具有不同的亚结构。分子动力学模拟的MUC1糖肽和肽揭示了构象偏好的区别。