Over the years, structural characterizations of α(2–8)-polysialic acid (polySia) in solution have produced inconclusive results. Efforts for obtaining detailed information in this important antigen have focused primarily on the α-linked residues and not on the distinctive characteristics of the terminal ones. The thermodynamically preferred anomeric configuration for the reducing end of sialic acids is β, which has the [I]CO₂^– group equatorial and the OH ([I]OH2) axial, while for all other residues the CO₂^– group is axial. We show that this purportedly minor difference has distinct consequences for the structure of α(2–8)-polySia near the reducing end, as the β configuration places the [I]OH2 in a favorable position for the formation of a hydrogen bond with the carboxylate group of the following residue ([II]CO₂^–). Molecular dynamics (MD) simulations predicted the hydrogen bond, which we subsequently directly detected by NMR. The combination of MD and residual dipolar couplings shows that the net result for the structure of Sia₂-βOH is a stable conformation with well-defined hydration and charge patterns, and consistent with experimental NOE-based hydroxyl and aliphatic inter-proton distances. Moreover, we provide evidence that this distinct conformation is preserved on Sia oligosaccharides, thus constituting a motif that determines the structure and dynamics of α(2–8)-polySia for at least the first two residues of the polymer. We suggest the hypothesis that this structural motif sheds light on a longtime puzzling observation for the requirement of 10 residues of α(2–8)-polySia in order to bind effectively to specific antibodies, about four units more than for analogous cases.

中文翻译：

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α(2–8)-聚唾液酸中的β-还原端构成了独特的结构基序


多年来，溶液中 α(2–8)-聚唾液酸 (polySia) 的结构表征一直没有得出结论。获取这一重要抗原详细信息的努力主要集中在 α-连接残基上，而不是末端残基的独特特征。唾液酸还原端的热力学首选异头构型是 β，其具有平轴的 [I]CO ₂ ^–基团和轴轴的 OH ([I]OH2)，而对于所有其他残基，CO ₂ ^–基团是轴轴的。我们表明，这种所谓的微小差异对还原端附近的 α(2–8)-polySia 结构具有明显的影响，因为 β 构型使 [I]OH2 处于与形成氢键的有利位置。以下残基的羧酸基团([II]CO ₂ ^– )。分子动力学 (MD) 模拟预测了氢键，我们随后通过 NMR 直接检测到了氢键。 MD和残余偶极耦合的组合表明，Sia ₂ -βOH结构的最终结果是具有明确水合和电荷模式的稳定构象，并且与基于实验NOE的羟基和脂肪族质子间距离一致。此外，我们提供的证据表明，这种独特的构象保留在Sia寡糖上，从而构成了一个基序，该基序决定了α(2-8)-polySia至少聚合物前两个残基的结构和动力学。 我们提出这样的假设，即该结构基序揭示了长期令人费解的观察结果，即需要 10 个 α(2-8)-polySia 残基才能有效结合特定抗体，比类似情况多大约四个单位。