Does Inter-Residue Hydrogen Bonding in β-(1→4)-Linked Disaccharides Influence Linkage Conformation in Aqueous Solution?
Does Inter-Residue Hydrogen Bonding in β-(1→4)-Linked Disaccharides Influence Linkage Conformation in Aqueous Solution?
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DOI：
10.1021/acs.jpcb.3c07448
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发表时间：
2024-02-28
影响因子：
3.3
通讯作者：
Serianni，Anthony S.
中科院分区：
文献类型：
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作者：
Zhang，Wenhui;Meredith，Reagan J.;Serianni，Anthony S.
用选择性~（13）C富集法制备了两种双糖，甲基β-d-半乳糖基-（1→4）-α-d-葡萄糖苷（1）和甲基β-d-半乳糖基-（1→4）-3-脱氧-α-d-核糖-己糖苷（3），以测定每种化合物中6种反式-O-糖苷J-偶联（2 JCOC，3 JCOCH和3 JCOCC）。用密度泛函理论（DFT）来参数化将这些J-偶联与α或β联系起来的类Karplus方程。对这两种键进行MA ′ AT分析，以确定每种二糖中α和β的平均值及其相关的圆标准偏差（CSD）。结果表明，在C3为1脱氧对连杆扭转角的平均值和摆动运动影响不大。这一发现意味着，如果在水溶液中，O3 H和1的O 5 ′之间的残基间氢键存在并持续存在，那么它在决定优选的键合构象方面几乎没有任何作用。氢键可能会降低优选键合几何形状的能量，但不会在任何明显程度上决定它。水溶液1-μs分子动力学模拟支持这一结论，也表明在脱氧二氢山梨醇3中，在溶液中取样几种构象不同的高能构象时，构象具有更大的灵活性。后者的构象数很低（3-14%），不能用MA ′ AT分析来验证。然而，如果MD模型是正确的，C3脱氧确实能够在更广泛的/ψ值范围内进行构象采样，但主要构象体中的连接构象在1和3中基本相同。
Two disaccharides, methyl β-d-galactopyranosyl-(1→4)-α-d-glucopyranoside (1) and methyl β-d-galactopyranosyl-(1→4)-3-deoxy-α-d-ribo-hexopyranoside (3), were prepared with selective13C-enrichment to allow measurement of six trans-O-glycosidicJ-couplings (2JCOC,3JCOCH, and3JCOCC) in each compound. Density functional theory (DFT) was used to parameterize Karplus-like equations that relate theseJ-couplings to eitherϕorψ.MA’ATanalysis was applied to both linkages to determine mean values ofϕandψin each disaccharide and their associated circular standard deviations (CSDs). Results show that deoxygenation at C3 of1has little effect on both the mean values and librational motions of the linkage torsion angles. This finding implies that, if inter-residue hydrogen bonding between O3H and O5′ of1is present in aqueous solution and persistent, it plays little if any role in dictating preferred linkage conformation. Hydrogen bonding may lower the energy of the preferred linkage geometry but does not determine it to any appreciable extent. Aqueous 1-μs MD simulation supports this conclusion and also indicates greater conformational flexibility in deoxydisaccharide3in terms of sampling several, conformationally distinct, higher-energy conformers in solution. The populations of these latter conformers are low (3–14%) and could not be validated byMA’ATanalysis. If the MD model is correct, however, C3 deoxygenation does enable conformational sampling over a wider range ofϕ/ψvalues, but linkage conformation in the predominant conformer is essentially identical in both1and3.