Simplified analogs of bryostatin with anticancer activity display greater potency for translocation of PKCdelta-GFP.
Structurally simplified analogs of bryostatin 1, a marine natural product in clinical trials for the treatment of cancer, have been shown to be up to 50 times more potent than bryostatin 1 at inducing the translocation of PKCdelta-GFP from the cytosol of rat basophilic leukemia (RBL) cells. The end distribution of the protein is similar for all three compounds, despite a significant difference in translocation kinetics. The potency of the compounds for inducing the translocation response appears to be only qualitatively related to their binding affinity for PKC, highlighting the importance of using binding affinity in conjunction with real-time measurements of protein localization for the pharmacological profiling of biologically active agents.
Baryza
Jeremy L
JL
Department of Chemistry, Stanford University, Stanford, CA 94305, USA.
Brenner
Stacey E
SE
Craske
Madeleine L
ML
Meyer
Tobias
T
Wender
Paul A
PA
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D054713:Bryostatins; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004705:Endocytosis / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000378:metabolism*; D007700:Kinetics; D007783:Lactones / Q000737:chemistry / Q000494:pharmacology*; D018942:Macrolides; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D015394:Molecular Structure; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D054713:Bryostatins; D007783:Lactones; D018942:Macrolides; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; C046785:bryostatin 1; D011493:Protein Kinase C