The conformation of the mannopyranosyl phosphate repeating unit of the capsular polysaccharide of Neisseria meningitidis serogroup A and its carba-mimetic,European Journal of Organic Chemistry

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The conformation of the mannopyranosyl phosphate repeating unit of the capsular polysaccharide of Neisseria meningitidis serogroup A and its carba-mimetic
European Journal of Organic Chemistry ( IF 2.5 ) Pub Date : 2018-08-17 , DOI: 10.1002/ejoc.201801003
Ilaria Calloni _{1,

2} , Luca Unione ₃ , Gonzalo Jiménez-Osés ₄ , Francisco Corzana ₄ , Linda Del Bino ₅ , Alessio Corrado _{5,

6} , Olimpia Pitirollo ₆ , Cinzia Colombo ₆ , Luigi Lay ₆ , Roberto Adamo ₅ , Jesús Jiménez-Barbero _{1,

2,

7}

Affiliation

Neisseria meningitidis serogroup A (MenA) is an aerobic diplococcal Gram‐negative bacterium responsible for epidemic meningitis disease. Its capsular polysaccharide (CPS) has been identified as the primary virulence factor of MenA. This polysaccharide suffers from chemical lability in water. Thus, the design and synthesis of novel and hydrolytically stable structural analogues of MenA CPS may provide additional tools for the development of therapies against this disease. In this context, the structural features of the natural phosphorylated monomer have been analyzed and compared to those of its carba‐analogue, where the endocyclic oxygen has been replaced by a methylene moiety. The lowest energy geometries of the different molecules have been calculated using a combination of quantum mechanical techniques and molecular dynamics simulations. The predicted results have been compared and validated using NMR experiments. The results indicate that the more stable designed glycomimetics may adopt the conformation adopted by the natural monomer, although they display a wider flexibility around the torsional degrees of freedom.

中文翻译：

脑膜炎奈瑟菌血清群 A 荚膜多糖的吡喃甘露糖基磷酸重复单元的构象及其模拟碳水化合物

脑膜炎奈瑟菌血清群 A (MenA) 是一种需氧双球菌革兰氏阴性菌，可导致流行性脑膜炎疾病。其荚膜多糖 (CPS) 已被确定为 MenA 的主要毒力因子。这种多糖在水中具有化学不稳定性。因此，MenA CPS 的新型水解稳定结构类似物的设计和合成可能为开发针对该疾病的疗法提供额外的工具。在这种情况下，对天然磷酸化单体的结构特征进行了分析，并将其与其碳水化合物类似物的结构特征进行了比较，其中环内氧已被亚甲基部分取代。使用量子力学技术和分子动力学模拟的组合计算了不同分子的最低能量几何形状。已使用核磁共振实验对预测结果进行了比较和验证。结果表明，更稳定的设计糖模拟物可能采用天然单体采用的构象，尽管它们在扭转自由度方面表现出更广泛的灵活性。

更新日期：2018-08-17

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