烷基链长对鞘氨醇激酶 2 选择性的影响。
Effect of alkyl chain length on sphingosine kinase 2 selectivity.
机构信息
Department of Chemistry, Virginia Tech, Blacksburg, VA 24061, USA.
出版信息
Bioorg Med Chem Lett. 2012 Nov 15;22(22):6817-20. doi: 10.1016/j.bmcl.2012.01.050. Epub 2012 Jan 26.
Abstract
The conversion of sphingosine to sphingosine-1-phosphate is catalyzed by sphingosine kinase (SphK), which has been implicated in disease states such as cancer and fibrosis. Because SphK exists as two different isoforms, SphK1 and SphK2, understanding the physiological function of each isoenzyme is important. Of the two isoenzymes, SphK2 is significantly less understood, which is evident by the lack of selective small molecule inhibitors. Building on our initial work that focused on the structure-activity relationship study on an FTY720-derived cylohexylamine scaffold, we report that varying the alkyl chain length on the hydrophobic tail can impart selectivity toward SphK2 over SphK1.
摘要
鞘氨醇到鞘氨醇-1-磷酸的转化由鞘氨醇激酶（SphK）催化，该酶已被牵涉到癌症和纤维化等疾病状态中。由于 SphK 存在两种不同的同工型，SphK1 和 SphK2，因此了解每种同工酶的生理功能很重要。在这两种同工酶中，SphK2 的了解明显较少，这可以从缺乏选择性的小分子抑制剂中得到证明。在我们最初专注于 FTY720 衍生的环己基胺支架的结构-活性关系研究的基础上，我们报告说改变疏水尾部的烷基链长度可以赋予对 SphK2 的选择性，而不是 SphK1。
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