N -Acetyl Side-Chain Conformation in Saccharides: Solution Models Obtained from MA’AT Analysis
N -Acetyl Side-Chain Conformation in Saccharides: Solution Models Obtained from MA’AT Analysis
复制标题
糖中的 N-乙酰侧链构象：从 MAâAT 分析中获得的解决方案模型
DOI：
10.1021/acs.joc.2c00189
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发表时间：
2022
期刊：
影响因子：
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通讯作者：
Serianni, Anthony S.
中科院分区：
文献类型：
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作者：
Meredith, Reagan J.;Tetrault, Timothy;Yoon, Mi-Kyung;Zhang, Wenhui;Carmichael, Ian;Serianni, Anthony S.
MA'AT分析已被用于模拟生物学上重要的GlcNAc和ManNAc单糖以及βGlcNAc-（1→4）-βGlcNAc二糖中N-乙酰基侧链的构象性质。进行密度泛函理论计算以获得参数化方程，该参数化方程将10个自旋耦合常数的大小和符号与GlcNAc和ManNAc的C2-N2键的构象相关联。其中六个方程与实验J-偶合一起用于模拟GlcNAc和ManNAc残基的C1-C2-N2-C1′扭转角（θ1），在水溶液中αGlcNAc和βGlcNAc的θ 1平均值分别为106°和116 °，圆标准偏差（CSD）为21-22°。与水分子动力学模拟结果吻合良好。参数空间图显示了数据的独特MA 'AT拟合，均方根偏差（<0.2 Hz）比MD模型反算的结果小两倍，表明MA' AT模型更好地拟合了实验J耦合。在βGlcNAc-（1→4）-βGlcNAc二糖中，环境对两个θ 1值的影响很小。MA'AT分析得出αManNAc在H2O/2 H2O中的θ 1平均值为249°，CSD为1019 °，两个值与MD一致。N-乙酰基侧链的MA' AT模型与先前获得的O-乙酰基侧链模型相似（J. Phys. Chem. B2017，121，66-77）。O-乙酰化和N-乙酰化都在构象上限制了C-O键或C-N键，相对于未取代化合物中的相同键。目前的工作证实的能力ofMA'AT分析，以揭示相对较小的变化，平均分子扭转角的解决方案，并提供了额外的证据，该方法作为一种实验工具，补充MD模拟。
MA’ATanalysis has been applied to model the conformational properties ofN-acetyl side-chains in biologically important GlcNAc and ManNAc monosaccharides and in a βGlcNAc-(1→4)-βGlcNAc disaccharide. Density functional theory calculations were conducted to obtain parameterized equations that relate the magnitudes and signs of 10 spin-coupling constants to conformations of the C2–N2 bonds of GlcNAc and ManNAc. Six of these equations were used with experimentalJ-couplings, measured in H2O/2H2O and DMSO-d6solvents in selectively13C-labeled compounds, to model the C1–C2–N2–C1′ torsion angle (θ1) in GlcNAc and ManNAc residues.MA’ATanalysis gave mean values of θ1of 106° for αGlcNAc and ∼116° for βGlcNAc residues, with circular standard deviations (CSDs) of 21–22° in aqueous solution, in excellent agreement with those obtained by aqueous molecular dynamics (MD) simulation. Parameter space plots revealed uniqueMA’ATfits of the data, and root mean squared deviations (<0.2 Hz) were twofold smaller than those back-calculated from MD models, indicating that theMA’ATmodels better fit the experimentalJ-couplings. Context effects on both θ1values were found to be small in a βGlcNAc-(1→4)-βGlcNAc disaccharide.MA’ATanalysis gave a mean value of θ1of 249° for αManNAc in H2O/2H2O, with a CSD of ∼19°, with both values in good agreement with MD.MA’ATmodels ofN-acetyl side-chains are similar to those obtained previously forO-acetyl side-chains (J. Phys. Chem. B2017,121,66–77). BothO- andN-acetylation conformationally constrain the C–O or C–N bonds relative to the same bonds in unsubstituted compounds. The present work confirms the ability ofMA’ATanalysis to reveal relatively small changes in mean molecular torsion angles in solution and provides additional evidence of the method as an experimental tool complementary to MD simulation.