Koehn Jordan T, Crick Dean C, Crans Debbie C
Chemistry Department, Cell and Molecular Biology Program, and Microbiology, Immunology, and Pathology Department, Colorado State University, Fort Collins, Colorado 80523, United States.
ACS Omega. 2018 Nov 5;3(11):14889-14901. doi: 10.1021/acsomega.8b02620. eCollection 2018 Nov 30.
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, , the causative agent of tuberculosis, uses predominantly MK-9(II-H) (saturated at the second isoprene unit) as its electron carrier and depends on the synthesis of MK-9(II-H) 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) and MK-3(II-H), and two novel fully saturated MK derivatives, MK-2(I,II-H) and MK-3(I,II,III-H).
甲萘醌（MKs）既含有一个氧化还原活性醌部分，又含有一个长度和饱和度不同的疏水重复异戊二烯侧链。这种独特的结构使MKs能够在一些原核生物的呼吸电子传递系统中发挥关键作用，通过在作为电子受体和供体的膜结合蛋白复合物之间穿梭电子和质子。具有部分饱和和完全饱和异戊二烯侧链的疏水MK分子存在于广泛的真细菌和古细菌中，MK类似物的结构变异在进化上是保守的，但人们对此了解甚少。例如，结核分枝杆菌主要使用MK-9（II-H）（在第二个异戊二烯单元处饱和）作为其电子载体，并依赖于MK-9（II-H）的合成在宿主巨噬细胞中存活。因此，具有部分饱和异戊二烯侧链的MKs可能代表一种新的毒力因子。天然存在的较长MKs非常疏水，而具有截短（即一至三个异戊二烯）异戊二烯侧链的MK类似物疏水性较低。这提高了它们在水溶液中的溶解度，便于对其结构和生物活性进行深入研究。我们展示了两种部分饱和的MK类似物MK-2（II-H）和MK-3（II-H）以及两种新型完全饱和的MK衍生物MK-2（I，II-H）和MK-3（I，II，III-H）的合成与表征。
