Total synthesis of two photoactivatable analogues of the growth-factor-like mediator sphingosine 1-phosphate

Differential interaction with protein targets

Xuequan Lu, Sandor Cseh, Hoe Sup Byun, Gabor Tigyi, Robert Bittman

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

The first synthesis of two photoreactive analogues of the lipid mediator and second messenger sphingosine 1-phosphate (S1P), [32P]-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 (S1P1) transfected into membranes of rat hepatoma cells and with plasma proteins were analyzed. The S1P1 receptor interacted in a specific manner with the benzophenone-containing ligand (KD = 84 ± 10 nM vs KD 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.

Original languageEnglish (US)
Pages (from-to)7046-7050
Number of pages5
JournalJournal of Organic Chemistry
Volume68
Issue number18
DOIs
StatePublished - Sep 5 2003

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Intercellular Signaling Peptides and Proteins
Lysosphingolipid Receptors
Proteins
Blood Proteins
Diazomethane
Ligands
Beam plasma interactions
Second Messenger Systems
Labeling
Rats
Carrier Proteins
Phosphates
sphingosine 1-phosphate
Membranes
Lipids
Plasmas

All Science Journal Classification (ASJC) codes

  • Organic Chemistry

Cite this

Total synthesis of two photoactivatable analogues of the growth-factor-like mediator sphingosine 1-phosphate : Differential interaction with protein targets. / Lu, Xuequan; Cseh, Sandor; Byun, Hoe Sup; Tigyi, Gabor; Bittman, Robert.

In: Journal of Organic Chemistry, Vol. 68, No. 18, 05.09.2003, p. 7046-7050.

Research output: Contribution to journalArticle

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AB - The first synthesis of two photoreactive analogues of the lipid mediator and second messenger sphingosine 1-phosphate (S1P), [32P]-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 (S1P1) transfected into membranes of rat hepatoma cells and with plasma proteins were analyzed. The S1P1 receptor interacted in a specific manner with the benzophenone-containing ligand (KD = 84 ± 10 nM vs KD 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.

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