Dramatic switching of protein kinase C agonist/antagonist activity by modifying the 12-ester side chain of phorbol esters.
J Am Chem Soc
; 124(36): 10658-9, 2002 Sep 11.
Article
em En
| MEDLINE
| ID: mdl-12207512
ABSTRACT
A dramatic switching of PKC agonist and antagonist activity was observed by modification of the hydrophilicity of the 12-ester side chain of phorbol. Thus, phorbol ester 4 that contains a glycol at the 12-ester chain demonstrated a pure and significant antagonist ability of PKC; however, 3 that contains an alkanol at the 12-ester chain demonstrated a potent PKC agonist activity. On the basis of the structural difference between 3 and 4 and results of the partition assay in the Hela cell/PBS buffer system, we propose that 4 acts as a translocation poison of the PKC-phorbol ester complex. The approach of controlling the agonist/antagonist activity of phorbol esters by the nature (i.e., hydrophilicity, charge, and rigidity, etc.) of the 12-ester chain may be very useful for developing selective PKC inhibitors and a potential pharmaceutical compound for anticancer therapies.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteína Quinase C
/
Ésteres de Forbol
/
Acetato de Tetradecanoilforbol
Limite:
Humans
Idioma:
En
Ano de publicação:
2002
Tipo de documento:
Article