title: Constrained azacyclic analogues of the immunomodulatory agent FTY720 as molecular probes for sphingosine 1-phosphate receptors.
abstract: 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 S1P receptors: while being inactive on S1P1 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.
authors.affiliation: Department of Chemistry, Université de Montréal, PO Box 6128, Station Centre-ville, Montréal, Que., Canada H3C 3J7. stephen.hanessian@umontreal.ca
authors.forename: Stephen
authors.initials: S
authors.lastname: Hanessian
authors.forename: Guillaume
authors.initials: G
authors.lastname: Charron
authors.forename: Andreas
authors.initials: A
authors.lastname: Billich
authors.forename: Danilo
authors.initials: D
authors.lastname: Guerini
mesh_terms: D000818:Animals; D001372:Aza Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*; D016466:CHO Cells / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002855:Chromatography, Thin Layer; D006224:Cricetinae; D003412:Cricetulus; D003593:Cytoplasm / Q000378:metabolism; D015195:Drug Design; D000068876:Fingolimod Hydrochloride; D006801:Humans; D007155:Immunologic Factors / Q000138:chemical synthesis* / Q000494:pharmacology*; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D015335:Molecular Probes / Q000138:chemical synthesis* / Q000494:pharmacology*; D010766:Phosphorylation; D011409:Propylene Glycols / Q000494:pharmacology*; D049349:Receptors, Lysosphingolipid / Q000187:drug effects*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D001372:Aza Compounds; D007155:Immunologic Factors; D007202:Indicators and Reagents; D015335:Molecular Probes; D011409:Propylene Glycols; D049349:Receptors, Lysosphingolipid; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine; D002118:Calcium