Absolute Configuration of Native Oligomeric Proanthocyanidins with Dentin Biomodification Potency.
Absolute Configuration of Native Oligomeric Proanthocyanidins with Dentin Biomodification Potency.
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DOI：
10.1021/acs.joc.6b02161
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发表时间：
2017-02-03
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影响因子：
--
通讯作者：
Pauli GF
中科院分区：
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作者：
Nam JW;Phansalkar RS;Lankin DC;McAlpine JB;Leme-Kraus AA;Vidal CM;Gan LS;Bedran-Russo A;Chen SN;Pauli GF
结构复杂的低聚原花青素（OPAC）是一种很有前途的仿生剂，能够通过分子间和微纤维间的交联来增强牙齿的大分子骨架。本研究建立了能够确定未衍生化OPAC的儿茶素型单体单元的绝对构型的分析方法。这保留了其生物学评价的能力，旨在了解OPAC和牙本质胶原之间不可避免的立体特异性相互作用。在牙本质生物活性测定（弹性模量、长期稳定性）的指导下，从马尾松树皮中发现了两种新的A型OPAC三聚体和四聚体，分别为表儿茶素-（2β→O→ 7，4 β →8）-表儿茶素-（2 β → O → 7，4 β→8）-儿茶素（5）和表儿茶素-（2β→O → 7，4 β→8）-表儿茶素-（2 β → O → 7，4 β→6）-表儿茶素-（2β→O→ 7，4 β→8）-儿茶素（6）。结合1D/2D NMR，HRESIMS，ECD，1H迭代全自旋分析（HiFSA）和规范不变原子轨道（GIAO）δ计算，我们展示了13 C NMR化学位移（非对映体构建块（A型二聚体））如何使高级低聚物5和6中单体单元的绝对构型的确定变得更加有效。总的来说，当要避免降解分析时，具有ECD参考数据的NMR提高了这些结构要求高的分子可获得的结构信息的水平。考虑到它们的众多和欺骗性的微妙，但3D有影响力的结构变化，这推进了OPAC化学空间的探测，以选择性地结合胶原和潜在的其他生物重要的生物大分子。
The structurally complex oligomeric proanthocyanidins (OPACs) are promising biomimetic agents, capable of strengthening the macromolecular backbone of teeth via intermolecular and intermicrofibrillar cross-linking. This study establishes analytical methods capable of determining the absolute configuration of the catechin-type monomeric units of underivatized OPACs. This preserves the capacity of their biological evaluation, aimed at understanding the inevitably stereo-specific interactions between the OPACs and dentin collagen. Guided by dental bioassays (modulus of elasticity, long-term stability), two new trimeric and tetrameric A-type OPACs were discovered as dentin biomodifiers from pine (Pinus massoniana) bark: epicatechin-(2β→O→7,4β→8)-epicatechin-(2β→O→7,4β→8)-catechin (5) and epicatechin-(2β→O→7,4β→8)-epicatechin-(2β→O→7,4β→6)-epicatechin-(2β→O→7,4β→8)-catechin (6), respectively. Combining 1D/2D NMR, HRESIMS, ECD, 1H iterative full spin analysis (HiFSA), and gauge-invariant atomic orbital (GIAO) δ calculations, we demonstrate how 13C NMR chemical shifts (diastereomeric building blocks (A-type dimers)) empower the determination of the absolute configuration of monomeric units in the higher oligomers 5 and 6. Collectively, NMR with ECD reference data elevates the level of structural information achievable for these structurally demanding molecules when degradation analysis is to be avoided. Considering their numerous and deceptively subtle, but 3D impactful, structural variations, this advances the probing of OPAC chemical spaces for species that bind selectively to collagenous and potentially other biologically important biomacromolecules.