A receptor model for tumor promoters: Rational superposition of teleocidins and phorbol esters

Journal Article · Wed Jun 01 04:00:00 EDT 1988 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.85.11.3688· OSTI ID:5512727

Itai, Akiko; Kato, Yuichi; Tomioka, Nobuo; Iitaka, Yoichi; Endo, Yasuyuki; Hasegawa, Masashi; Shudo, Koichi; Fujiki, Hirota; Sakai, Shinichiro ^[1]

---

1. Univ. of Tokyo (Japan)

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.

• OSTI ID: 5512727
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (USA) Vol. 85:11; ISSN 0027-8424; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
CARCINOGENESIS
CARCINOGENS
COMPUTER GRAPHICS
ESTERS
MATHEMATICAL MODELS
MEMBRANE PROTEINS
ORGANIC COMPOUNDS
PATHOGENESIS
PATIENTS
PHORBOL ESTERS
PROMOTERS
PROTEINS
RECEPTORS
STRUCTURE-ACTIVITY RELATIONSHIPS
TUMOR PROMOTERS