The creation of caged molecules involves the attachment of protecting groups to biologically active compounds such as ligands, substrates, and drugs that can be removed under specific conditions. Photoremovable caging groups are the most common due to their ability to be removed with high spatial and temporal resolution. Here, the synthesis and photochemistry of two caged inhibitors of protein farnesyltransferase, BHQ-FTI and Bhc-FTI will be described. We will then show that these molecules can be photolyzed with UV light to release FTI that inhibits Ras farnesylation (observed via Western blot analysis), Ras membrane localization (detected by confocal microscopy), and downstream signaling (fibroblast morphology). Finally, we will show that Bhc-FTI can be uncaged by two-photon excitation to produce FTI at levels sufficient to inhibit Ras localization.

Photochemical modulation of Ras-mediated signal transduction using caged farnesyltransferase inhibitors: Activation via one- and two-photon excitation

241st National Meeting (2011)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.