Synthesis and Characterization of Partially and Fully Saturated Menaquinone Derivatives
Synthesis and Characterization of Partially and Fully Saturated Menaquinone Derivatives
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DOI：
10.1021/acsomega.8b02620
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发表时间：
2018-11-01
期刊：
影响因子：
4.1
通讯作者：
Crans, Debbie C.
中科院分区：
文献类型：
--
作者：
Koehn, Jordan T.;Crick, Dean C.;Crans, Debbie C.
甲基萘醌（MK）含有氧化还原活性醌部分和不同长度和饱和度的疏水重复异戊二烯基侧链。这种特征性结构允许MK通过在膜结合蛋白质复合物之间穿梭电子和质子而在一些原核生物的呼吸电子传递系统中发挥关键作用，所述膜结合蛋白质复合物充当电子受体和供体。具有部分和完全饱和异戊二烯基侧链的疏水MK分子在广泛的真细菌和古细菌中发现，MK类似物的结构变异在进化上是保守的，但知之甚少。例如，结核病的病原体结核分枝杆菌主要使用MK-9（II-H-2）（在第二个异戊二烯单元处饱和）作为其电子载体，并且依赖于MK 9（II-H-2）的合成来在宿主巨噬细胞中存活。因此，具有部分饱和异戊二烯基侧链的MK可能代表一种新的毒力因子。天然存在的较长MK是非常疏水的，而具有截短（即，1 - 3个异戊二烯）异戊二烯基侧链疏水性较低。这提高了它们在水溶液中的溶解度，允许对其结构和生物活性进行严格的研究。本文报道了两种部分饱和的MK类似物MK-2（II-H-2）和MK-3（II-H-2）以及两种新的完全饱和的MK衍生物MK-2（I，II-H-4）和MK-3（I，II-III-H-6）的合成和表征。
Menaquinones (MKs) contain both a redox active quinone moiety and a hydrophobic repeating isoprenyl side chain of varying lengths and degrees of saturation. This characteristic structure allows MKs to play a key role in the respiratory electron transport system of some prokaryotes by shuttling electrons and protons between membrane-bound protein complexes, which act as electron acceptors and donors. Hydrophobic MK molecules with partially and fully saturated isoprenyl side chains are found in a wide range of eubacteria and archaea, and the structural variations of the MK analogues are evolutionarily conserved but poorly understood. For example, Mycobacterium tuberculosis, the causative agent of tuberculosis, uses predominantly MK-9(II-H-2) (saturated at the second isoprene unit) as its electron carrier and depends on the synthesis of MK9(II-H-2) for survival in host macrophages. Thus, MKs with partially saturated isoprenyl side chains may represent a novel virulence factor. Naturally occurring longer MKs are very hydrophobic, whereas MK analogues that have a truncated (i.e., one to three isoprenes) isoprenyl side chain are less hydrophobic. This improves their solubility in aqueous solutions, allowing rigorous study of their structure and biological activity. We present the synthesis and characterization of two partially saturated MK analogues, MK-2(II-H-2) and MK-3(II-H-2), and two novel fully saturated MK derivatives, MK-2(I,II-H-4) and MK-3(I,II-III-H-6).