PHOTOLABILE DERIVATIVES OF INDOLE ALKALOID TUMOR PROMOTER TELEOCIDINS- SYNTHESIS, BIOLOGICAL-ACTIVITIES AND PHOTOAFFINITY-LABELING STUDIES

New photolabile teleocidin derivatives (Az-A-1, Az-C7 and Az-C2) were synthesized and examined by three in vitro bioassays related to tumor- promoting activity. Az-A-1 (15) and two epimers of Az-C7 (11a, 11b) we re approximately 10 to 100-fold more active than (-)-indolactam-V(1), the fundamental structure of teleocidins. Synthesis of the H-3-labeled probes with specific activity of more than 40 Ci/mmol was achieved by use of commercially available H-3-labeled succinimidyl-4-azidobenzoat e. Specific binding of [H-3]Az-A-1 and [H-3]Az-C7 to the mouse epiderm al particulate fraction, the target tissue of teleocidins, was saturab le at approximately 20nM. Photoaffinity labeling on the particulate fr action using [H-3]Az-A-1 supported the recent hypothesis that the alky l chain at position of teleocidins is involved in the interaction with the phospholipids close to the receptor site. SDS gel electrophoresis of the photolabeled particulate fraction suggested the existence of t wo proteins (ca.30 and 50kD) specifically photolabeled by [H-3]Az-A-1 and [H-3]Az-C7. However, no specific labeling was detected at the 70 t o 80kD region, which corresponded to protein kinase C, a well-characte rized receptor for tumor promoters.