2-deoxy-L-fucosyl-2-deoxy-L-fucosyl-rhodosaminyl-aklavinone

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 蒽环类药物
• 英文名称: 2-deoxy-L-fucosyl-2-deoxy-L-fucosyl-rhodosaminyl-aklavinone
• 英文别名: (1R,2R,4S)-4-{[2,6-dideoxy-alpha-L-lyxo-hexopyranosyl-(1->4)-2,6-dideoxy-alpha-L-lyxo-hexopyranosyl-(1->4)-2,3,6-trideoxy-3-(dimethylazaniumyl)-alpha-L-lyxo-hexopyranosyl]oxy}-2-ethyl-2,7-dihydroxy-1-(methoxycarbonyl)-6,11-dioxo-1,2,3,4,6,11-hexahydrotetracen-5-olate；(1R,2R,4S)-4-[(2R,4S,5S,6S)-5-[(2S,4S,5S,6S)-5-[(2S,4S,5S,6S)-4,5-dihydroxy-6-methyloxan-2-yl]oxy-4-hydroxy-6-methyloxan-2-yl]oxy-4-(dimethylazaniumyl)-6-methyloxan-2-yl]oxy-2-ethyl-2,7-dihydroxy-1-methoxycarbonyl-6,11-dioxo-3,4-dihydro-1H-tetracen-5-olate
• 化学式: C₄₂H₅₅NO₁₆
• 分子量: 829.896
• InChiKey: DEGUCPPGAZTULS-UJSHPDKWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  59
• 可旋转键数：
  10
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  245
• 氢给体数：
  6
• 氢受体数：
  16

反应信息

• 作为产物：
  描述：

  aklavin 、 thymidine 5'-(2,6-dideoxy-β-L-lyxo-hexopyranosyl diphosphate) 在 magnesium chloride AknS 、 AknT 、 AknK 作用下， 以 二甲基亚砜 为溶剂， 反应 6.0h， 生成 2-deoxy-L-fucosyl-2-deoxy-L-fucosyl-rhodosaminyl-aklavinone 、 阿克那霉素 S
  参考文献：
  名称：

  AknS/AknT 糖基化复合物对红多胺转移的表征及其在重建阿克拉霉素 A 生物合成途径中的应用

  摘要：

  具有抗肿瘤活性的蒽环类天然产物（如阿克拉霉素 A）的四环核心在生物合成过程中通过区域选择性糖基化进行定制。我们报告了 TDP-L-罗多糖胺的首次合成，并证明糖基转移酶 AknS 将 L-罗多糖胺转移到苷元以启动侧链三糖的构建。伙伴蛋白 AknT 将用于 L-紫多糖胺转移的 AknS 周转率提高了 200 倍。AknT 不影响 Km，而是影响 kcat。使用这些数据，我们建议 AknT 导致 AknS 的构象变化，从而稳定过渡状态并最终增强转移。当随后的糖基转移酶 AknK 及其底物 TDP-L-岩藻糖也加入到苷元中时，

  DOI：

  10.1021/ja072909o

文献信息

• AknK Is an <scp>l</scp>-2-Deoxyfucosyltransferase in the Biosynthesis of the Anthracycline Aclacinomycin A
  作者：Wei Lu、Catherine Leimkuhler、Markus Oberthür、Daniel Kahne、Christopher T. Walsh

  DOI：10.1021/bi035945i

  日期：2004.4.1

  The antitumor drug aclacinomycin A is a representative member of the anthracycline subgroup that contains a C-7-O-trisaccharide chain composed Of L-2-deoxysugars. The sugar portion of the molecule, which greatly affects its biological activity, is assembled by dedicated glycosyltransferases; however, these enzymes have not been well-studied. Here we report the heterologous expression and purification of one of these enzymes, AknK, as well as the preparation of dTDP-L-2-deoxysugar donors, dTDP-L-2-deoxyfucose and dTDP-L-daunosamine, and the monoglycosyl aglycone, rhodosaminyl aklavinone. Our experiments show that AknK catalyzes the addition of the second sugar to the chain, using TDP-L-2-deoxyfucose and rhodosaminyl aklavinone, to create the L-2-deoxyfucosyl-L-rhodosaminyl aklavinone. AknK also accepts an alternate dTDP-L-sugar, dTDP-L-daunosamine, and other monoglycosylated anthracyclines, including daunomycin, adriamycin, and idarubicin, to build alternate disaccharides on variant anthracycline backbones. Remarkably, AknK also catalyzes a tandem addition of a second L-2-deoxyfucosyl moiety, albeit with reduced activity, to the natural disaccharide chain to produce L-deoxyfucosyl-L-deoxyfucosyl-L-rhodosaminyl aklavinone, a variant of the natural aclacinomycin A. These results demonstrate that AknK may be a useful enzyme for the chemoenzymatic synthesis of anthracycline variants.
• Characterization of Rhodosaminyl Transfer by the AknS/AknT Glycosylation Complex and Its Use in Reconstituting the Biosynthetic Pathway of Aclacinomycin A
  作者：Catherine Leimkuhler、Micha Fridman、Tania Lupoli、Suzanne Walker、Christopher T. Walsh、Daniel Kahne

  DOI：10.1021/ja072909o

  日期：2007.8.1

  The tetracyclic core of anthracycline natural products with antitumor activity such as aclacinomycin A are tailored during biosynthesis by regioselective glycosylation. We report the first synthesis of TDP-L-rhodosamine and demonstrate that the glycosyltransferase AknS transfers L-rhodosamine to the aglycone to initiate construction of the side-chain trisaccharide. The partner protein AknT accelerates

  具有抗肿瘤活性的蒽环类天然产物（如阿克拉霉素 A）的四环核心在生物合成过程中通过区域选择性糖基化进行定制。我们报告了 TDP-L-罗多糖胺的首次合成，并证明糖基转移酶 AknS 将 L-罗多糖胺转移到苷元以启动侧链三糖的构建。伙伴蛋白 AknT 将用于 L-紫多糖胺转移的 AknS 周转率提高了 200 倍。AknT 不影响 Km，而是影响 kcat。使用这些数据，我们建议 AknT 导致 AknS 的构象变化，从而稳定过渡状态并最终增强转移。当随后的糖基转移酶 AknK 及其底物 TDP-L-岩藻糖也加入到苷元中时，