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还原末端构成独特的结构基序

多年来，溶液中α（2-8）-聚唾液酸（polySia）的结构表征产生了不确定的结果。在重要的抗原中获得详细信息的努力主要集中在α-连接的残基上，而不是末端残基的独特特征上。对于唾液酸还原末端热力学优选的异头构型为β，其具有[I] CO ₂ ^-基团赤道和OH（[I] OH 2）的轴向，而对于所有其它残基的CO ₂ ^-组是轴向的。我们表明，据称较小的差异对还原端附近的α（2-8）-polySia的结构具有明显的影响，因为β构型使[I] OH2处于与氢键形成氢键的有利位置。以下残基（[II] CO ₂ ^–）的羧酸根。分子动力学（MD）模拟预测了氢键，随后我们通过NMR直接检测到了氢键。MD和残余偶极耦合的结合表明，Sia ₂结构的最终结果-βOH是稳定的构象，具有明确的水合和电荷模式，并且与实验性基于NOE的羟基和脂肪族质子间距离保持一致。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，因此构成了一个基序，该基序决定了至少聚合物的前两个残基的α（2-8）-polySia的结构和动力学。我们提出这样的假设，即这种结构基序为长时间困惑的观察提供了启示，该观察需要10个残基的α（2-8）-polySia才能有效结合特异性抗体，比类似情况要多四个单位。