Constrained azacyclic analogues of the immunomodulatory agent FTY720 as molecular probes for sphingosine 1-phosphate receptors
Constrained azacyclic analogues of the immunomodulatory agent FTY720 as molecular probes for sphingosine 1-phosphate receptors
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DOI：
10.1016/j.bmcl.2006.10.014
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发表时间：
2007-01-15
影响因子：
2.7
通讯作者：
Guerini, Danilo
中科院分区：
文献类型：
--
作者：
Hanessian, Stephen;Charron, Guillaume;Guerini, Danilo
以D-焦谷氨酸和L-焦谷氨酸为起始原料，合成了FTY720的约束氮环类似物。一种对映体被证明是鞘氨醇激酶2的底物，其磷酸化效率是FTY720的4倍。在相应的磷酸盐中，有两种在与SIPI和S1P3受体结合方面具有不同寻常的特异性：它们在SIPI和S1P3上不起作用，但在S1P4和S1P5上起到了强有力的激动剂的作用。这些磷酸盐可能有助于探索这些受体的生物学和结合部位。(C)2006爱思唯尔有限公司。保留所有权利。
Constrained azacyclic analogues of FTY720 were prepared starting with D- and L-pyroglutamic acids. One enantiomer was shown to be a substrate for sphingosine kinase 2, being phosphorylated 4-fold more efficiently than FTY720. Among the corresponding phosphates, two were found to have unusual specificity in binding to SIP receptors: while being inactive on SIPI and S1P3, they acted as potent agonists on S1P4 and S1P5. The phosphates may be useful to explore the biology and binding site of these receptors. (c) 2006 Elsevier Ltd. All rights reserved.