Chemical Transformation of B- to A-type Proanthocyanidins and 3D Structural Implications

IF 3.3 2区 生物学 Q2 CHEMISTRY, MEDICINAL
Shu-Xi Jing, Connor M. McDermott, Parker L. Flanders, Mariana Reis-Havlat, Shao-Nong Chen, Ana K. Bedran-Russo, James B. McAlpine, Elizabeth A. Ambrose and Guido F. Pauli*, 
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Abstract

In nature, proanthocyanidins (PACs) with A-type linkages are relatively rare, likely due to biosynthetic constraints in the formation of additional ether bonds to be introduced into the more common B-type precursors. However, A-type linkages confer greater structural rigidity on PACs than do B-type linkages. Prior investigations into the structure–activity relationships (SAR) describing how plant-derived PACs with B- and complex AB-type linkages affect their capacity for dentin biomodification indicate that a higher ratio of double linkages leads to a greater interaction with dentin type I collagen. Thus, A-type PACs emerge as particularly intriguing candidates for interventional functional biomaterials. This study employed a free-radical-mediated oxidation using DPPH to transform trimeric and tetrameric B-type PACs, 2 and 4, respectively, into their exclusively A-type linked analogues, 3 and 5, respectively. The structures and absolute configurations of the semisynthetic products, including the new all-A-type tetramer 5, were determined by comprehensive spectroscopic analysis. Additionally, molecular modeling investigated the conformational characteristics of all trimers and tetramers, 15. Our findings suggest that the specific interflavan linkages significantly impact the flexibility and low-energy conformations of the connected monomeric units, which conversely can affect the bioactive conformations relevant for dentin biomodification.

Abstract Image

Abstract Image

B 型原花青素到 A 型原花青素的化学转化及其三维结构影响
在自然界中,具有 A 型连接的原花青素(PAC)相对罕见,这可能是由于生物合成过程中需要在更常见的 B 型前体中引入额外的醚键。然而,与 B 型连接相比,A 型连接赋予 PAC 更大的结构刚性。之前对具有 B 型和复杂 AB 型连接的植物源 PAC 如何影响其牙本质生物改性能力的结构-活性关系(SAR)进行的研究表明,双连接的比例越高,与牙本质 I 型胶原的相互作用就越大。因此,A 型 PAC 成为介入性功能生物材料中特别令人感兴趣的候选材料。本研究利用自由基介导的 DPPH 氧化作用,将三聚体和四聚体的 B 型 PAC(分别为 2 和 4)分别转化为纯 A 型连接的类似物(分别为 3 和 5)。通过综合光谱分析确定了半合成产物(包括新的全 A 型四聚体 5)的结构和绝对构型。此外,分子建模研究了所有三聚体和四聚体 1-5 的构象特征。我们的研究结果表明,特定的黄烷间连接会显著影响连接单体单元的灵活性和低能构象,而这反过来又会影响与牙本质生物改性相关的生物活性构象。
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来源期刊
CiteScore
9.10
自引率
5.90%
发文量
294
审稿时长
2.3 months
期刊介绍: The Journal of Natural Products invites and publishes papers that make substantial and scholarly contributions to the area of natural products research. Contributions may relate to the chemistry and/or biochemistry of naturally occurring compounds or the biology of living systems from which they are obtained. Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin. When new compounds are reported, manuscripts describing their biological activity are much preferred. Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin.
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