Synthesis and bioactivity of photolabile sirolimus (rapamycin) analogs

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 vivo 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).