title: A receptor model for tumor promoters: rational superposition of teleocidins and phorbol esters.
abstract: Four 12-O-tetradecanoyl-13-O-acetylphorbol-type tumor promoters--teleocidin, phorbol ester, aplysiatoxin, and ingenol ester--are superposed in an attempt to understand their common biological activity on the assumption that they may bind to the same receptor site. A method using three-dimensional computer graphics was applied for superposing molecules and receptor mapping. The main feature of the method is that molecules are superposed in terms of spatial arrangement of physical and chemical properties but not in terms of the atomic positions as in conventional methods. This led to successful extraction of common structural features required for potent tumor-promoting activity: two hydrogen donors, a hydrogen acceptor, and a large lipophilic group. Their mutual spatial arrangements are most important for biological activity.
mesh_terms: D029742:Caenorhabditis elegans Proteins; D002273:Carcinogens; D002352:Carrier Proteins; D003196:Computer Graphics; D004224:Diterpenes; D006860:Hydrogen Bonding; D008235:Lyngbya Toxins; D008968:Molecular Conformation; D011493:Protein Kinase C; D011955:Receptors, Drug; D012995:Solubility; D013329:Structure-Activity Relationship; D013755:Tetradecanoylphorbol Acetate
chemical_list: D029742:Caenorhabditis elegans Proteins; D002273:Carcinogens; D002352:Carrier Proteins; D004224:Diterpenes; D008235:Lyngbya Toxins; D011955:Receptors, Drug; C027777:ingenol ester receptor; C083141:phorbol ester binding protein; C027776:phorbol ester receptor; C022176:teleocidins; C006610:aplysiatoxin; C056099:3-O-tetradecanoylingenol; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate