SYNTHESIS AND PROPERTIES OF PHOTOACTIVATABLE PHOSPHOLIPID DERIVATIVESDESIGNED TO PROBE THE MEMBRANE-ASSOCIATE DOMAINS OF PROTEINS

The total syntheses of photoactivatable phospholipidic probes 1 and 2 are described. These probes contain either an aryldiazonium function a t their polar head (probes la and Ib) or an diazocyclohexadienonyl gro up attached to the end of one fatty acid side chain (probe 2) and have been designed to probe the lipid/water interface and the hydrophobic core of the membrane, respectively. The synthetic schemes include the possibility of incorporating a radio-labeled atom (tritium) for furthe r labeling investigations. Both probes were stable in the dark under p hysiological conditions and could be efficiently photodecomposed at wa velengths above 300 nm, leading to the generation of highly reactive s pecies, aryl cations and cyclohexadienonyl carbene, respectively. In a ddition, these probes displayed UV-absorption spectra which are compat ible with tryptophan-mediated energy transfer photoactivation, which c an lead potentially to an efficient mapping of the membrane-associate protein domains.