Carotenuto Alfonso, D'Ursi Anna Maria, Mulinacci Barbara, Paolini Ilaria, Lolli Francesco, Papini Anna Maria, Novellino Ettore, Rovero Paolo
Department of Pharmaceutical and Toxicological Chemistry, University of Naples Federico II, I-80131 Naples, Italy.
J Med Chem. 2006 Aug 24;49(17):5072-9. doi: 10.1021/jm060117j.
Sera from patients suffering from autoimmune disorders often contain multiple types of autoantibodies, some of which can be exclusive of a disease and thus used as biomarkers for diagnosis. Identification of these autoantibodies, as disease biomarkers, should be achieved using native antigens in simple biological assays. However, posttranslational modifications, such as glycosylation, may play a fundamental role for specific autoantibody recognition. In line with these observations, we described synthetic glycopeptides able to detect high autoantibody titers in sera of patients affected by multiple sclerosis, an inflammatory, demyelinating disease of the central nervous system. We describe here the conformation-activity relationship of a focused library of glycopeptides based on structural diversity, with the aim of defining the structural requirements for the interaction of these glycopeptide antigens with specific autoantibodies. The final goal is the optimization of an antigenic probe for multiple sclerosis, to be used in the development of a simple diagnostic test based on an immunoenzymatic assay. The reported results clearly indicate that glycopeptides able to reveal high antibody titers in multiple sclerosis sera are characterized by a type I' beta-turn around the minimal epitope Asn(Glc), which allows an efficient exposure of this moiety to antibodies interactions, in the context of a solid-phase immunoenzymatic assay.
自身免疫性疾病患者的血清中通常含有多种自身抗体，其中一些可能是某种疾病所特有的，因此可作为诊断的生物标志物。作为疾病生物标志物，这些自身抗体的鉴定应在简单的生物学检测中使用天然抗原。然而，翻译后修饰，如糖基化，可能在特定自身抗体识别中起关键作用。基于这些观察结果，我们描述了能够检测多发性硬化症患者血清中高自身抗体滴度的合成糖肽，多发性硬化症是一种中枢神经系统的炎症性脱髓鞘疾病。我们在此描述了基于结构多样性的糖肽聚焦文库的构象-活性关系，目的是确定这些糖肽抗原与特定自身抗体相互作用的结构要求。最终目标是优化用于多发性硬化症的抗原探针，以用于基于免疫酶测定的简单诊断测试的开发。报道的结果清楚地表明，能够在多发性硬化症血清中显示高抗体滴度的糖肽的特征是在最小表位Asn(Glc)周围有一个I'型β-转角，这使得该部分在固相免疫酶测定的背景下能够有效地暴露于抗体相互作用中。
