Conformational Behaviour of Azasugars Based on Mannuronic Acid.
Conformational Behaviour of Azasugars Based on Mannuronic Acid.
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基于甘露糖醛酸的 Azasugar 的构象行为。
DOI：
10.1002/cbic.201700080
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发表时间：
2017
期刊：
影响因子：
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通讯作者：
Van Rijssel ER
中科院分区：
文献类型：
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作者：
Van Rijssel ER
合成了一组基于甘露糖醛酸的亚氨基糖，由 1-脱氧甘露诺吉米星 (DMJ) 的 C-5-羧酸、甲酯和酰胺类似物组成，并研究了它们的 pH 依赖性构象行为。在酸性条件下，甲酯和羧酸采用“倒置”1C4chair 构象，而不是在碱性 pH 条件下采用“正常”4C1chair 构象。这种构象变化可以用环取代基的立体电子效应来解释，并且它与甘露糖醛酸酯氧碳鎓离子的行为相似。由于这种溶液相行为，甘露糖醛酸酯 azasugar 被检查为 CaulobacterGH47 甘露糖苷酶的抑制剂，该酶通过 3H4 过渡态的反应行程水解其底物。没有观察到甘露糖醛酸酯 azasugar 的结合，但获得了 DMJ⋅CkGH47 复合物的亚原子分辨率数据，显示了 DMJ 抑制剂的两种构象 - 3S1 和 1C4。
A set of mannuronic‐acid‐based iminosugars, consisting of the C‐5‐carboxylic acid, methyl ester and amide analogues of 1deoxymannorjirimicin (DMJ), was synthesised and their pH‐dependent conformational behaviour was studied. Under acidic conditions the methyl ester and the carboxylic acid adopted an “inverted”1C4chair conformation as opposed to the “normal”4C1chair at basic pH. This conformational change is explained in terms of the stereoelectronic effects of the ring substituents and it parallels the behaviour of the mannuronic acid ester oxocarbenium ion. Because of this solution‐phase behaviour, the mannuronic acid ester azasugar was examined as an inhibitor for aCaulobacterGH47 mannosidase that hydrolyses its substrates by way of a reaction itinerary that proceeds through a3H4transition state. No binding was observed for the mannuronic acid ester azasugar, but sub‐atomic resolution data were obtained for the DMJ⋅CkGH47 complex, showing two conformations—3S1and1C4—for the DMJ inhibitor.