Total synthesis of two photoactivatable analogues of the growth-factor-like mediator sphingosine 1-phosphate: differential interaction with protein targets.
Total synthesis of two photoactivatable analogues of the growth-factor-like mediator sphingosine 1-phosphate: differential interaction with protein targets.
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DOI：
10.1021/jo034828q
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发表时间：
2003-08
期刊：
影响因子：
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通讯作者：
Xuequan Lu;S. Cseh;H. Byun;G. Tigyi;R. Bittman
中科院分区：
文献类型：
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作者：
Xuequan Lu;S. Cseh;H. Byun;G. Tigyi;R. Bittman
首次合成了两个光反应类似物，即脂质介体和第二信使1-磷酸鞘氨醇(S1P)，[(32)P]标记的(2S，3R)-14-O-(4‘-苯甲酰苯基)-和(2S，3R)-14-O-((4’-trifluoromethyldiazirinyl)phenyl)-(4E)-tetradecenyl-2-amino-3-hydroxy-1-phosphate，。分析了这些探针与S1P-1受体(S1P(1))的相互作用以及与血浆蛋白的相互作用。S1P(1)受体与二苯甲酮配体以一种特定的方式相互作用(K(D)=84+/-10 nM与K(D)，当S1P=36+/-2 nM时，K(D)=84+/-10 nM)；相反，没有发现S1P(1)与含二氮杂环的配体有饱和的特异性结合。然而，两种探针标记血浆蛋白的模式相同，表明S1P药效团的不同部分支持S1P与其受体和血浆载体蛋白的相互作用。
The first synthesis of two photoreactive analogues of the lipid mediator and second messenger sphingosine 1-phosphate (S1P), [(32)P]-labeled (2S,3R)-14-O-(4'-benzoylphenyl)- and (2S,3R)-14-O-((4'-trifluoromethyldiazirinyl)phenyl)-(4E)-tetradecenyl-2-amino-3-hydroxy-1-phosphate, is described. The interactions of these probes with the S1P type-1 receptor (S1P(1)) transfected into membranes of rat hepatoma cells and with plasma proteins were analyzed. The S1P(1) receptor interacted in a specific manner with the benzophenone-containing ligand (K(D) = 84 +/- 10 nM vs K(D) for S1P = 36 +/- 2 nM); in contrast, no saturable specific binding was found with the diazirine-containing ligand. However, the same pattern was found for labeling of plasma proteins by both probes, indicating that different parts of the S1P pharmacophore underlie the interaction of S1P with its receptor and plasma carrier proteins.