Several photolabile sirolimus analogs have been synthesized. All ot the compounds showed an antiproliferative effect in a mitogen-induced thymocyte proliferation assay. Compounds 3 and 4 were shown to be equipotent to sirolimus in a murine skin allograft model; they should thus be useful for investigating the in viva details of the signal transduction pathway(s) modulated by sirolimus. The immunosuppressive effect of analogs 3-5 is corroborated by their ability, as part of an FKBP12 complex, to bind a sirolimus effector protein (SEP).
Breakdown products of sphingolipids are involved in cell regulaion and exhibit a wide variety of activities related to signal transduction. The backbone of sphingolipids are the sphingosines which have two stereogenic centers. A general, rapid, chemical/chiroptical micromethod based on the bichromophoric CD exciton chirality principle was developed to distinguish all four possible stereoisomers nonambiguously at a level of ca. 1 microgram.