Bracco Imaging SpA-CRB Trieste, AREA Science Park, Building Q, SS 14, km 163.5, Basovizza, 34149 Trieste, Italy.
Carbohydr Res. 2012 Apr 1;351:114-20. doi: 10.1016/j.carres.2012.01.009. Epub 2012 Jan 28.
The present work aims at understanding the structural basis of the biological recognition of Tn antigen (GalNAc-α-O-L-Ser), a specific epitope expressed by tumor cells, and the role of its amino acidic moiety in the interaction with its receptor (the isolectin B4 extracted from Vicia villosa). An NMR structural characterization of the α and β anomers, based on J couplings and molecular modeling revealed a structure in very good agreement with data reported in literature for variants of the same molecules. In order to demonstrate the involvement of the amino acid in the ligand-receptor recognition, also GalNAc-α-O-D-Ser was studied; the change in the stereochemistry is in fact expected to impact on the interaction only in case the serine is part of the epitope. Relaxation properties in the presence of the receptor clearly indicated a selective recognition of the natural L form, probably due to the formation of a water-mediated hydrogen bond with Asn 129 of the protein.
本工作旨在研究 Tn 抗原（GalNAc-α-O-L-Ser）的生物识别的结构基础，该抗原是肿瘤细胞表达的特定表位，以及其氨基酸部分在与受体（从野豌豆中提取的同工凝集素 B4）相互作用中的作用。基于 J 耦合和分子建模对 α 和 β 两种异头物的 NMR 结构特征进行了研究，结果表明，所得到的结构与文献中报道的相同分子变体的结构非常吻合。为了证明氨基酸在配体-受体识别中的作用，还研究了 GalNAc-α-O-D-Ser；事实上，只有当丝氨酸是表位的一部分时，立体化学的变化才有望仅影响相互作用。在受体存在的情况下，弛豫特性清楚地表明了对天然 L 形式的选择性识别，这可能是由于与蛋白质的 Asn129 形成了水介导的氢键。
