Open AccessA receptor model for tumor promoters: rational superposition of teleocidins and phorbol esters.
Author(s) -
Akiko Itai,
Yuichi Kato,
Nobuo Tomioka,
Yōichi Iitaka,
Yasuyuki Endo,
Masashi Hasegawa,
Koichi Shudo,
Hirota Fujiki,
Shinichiro Sakai
Publication year - 1988
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.85.11.3688
Subject(s) - phorbol ester , chemistry , superposition principle , acceptor , molecule , receptor , stereochemistry , biochemistry , combinatorial chemistry , enzyme , mathematics , physics , organic chemistry , protein kinase c , mathematical analysis , condensed matter physics
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.