Membrane-surface anchoring of charged diacylglycerol-lactones correlates with biological activities.
Chembiochem
; 11(14): 2003-9, 2010 Sep 24.
Article
in En
| MEDLINE
| ID: mdl-20715268
ABSTRACT
Synthetic diacylglycerol-lactones (DAG-lactones) are effective modulators of critical cellular signaling pathways, downstream of the lipophilic second messenger diacylglycerol, that activate a host of protein kinase C (PKC) isozymes and other nonkinase proteins that share similar C1 membrane-targeting domains with PKC. A fundamental determinant of the biological activity of these amphiphilic molecules is the nature of their interactions with cellular membranes. This study examines the biological properties of charged DAG-lactones exhibiting different alkyl groups attached to the heterocyclic nitrogen of an α-pyridylalkylidene chain, and particularly the relationship between membrane interactions of the substituted DAG-lactones and their respective biological activities. Our results suggest that bilayer interface localization of the N-alkyl chain in the R(2) position of the DAG-lactones inhibits translocation of PKC isoenzymes onto the cellular membrane. However, the orientation of a branched alkyl chain at the bilayer surface facilitates PKC binding and translocation. This investigation emphasizes that bilayer localization of the aromatic side residues of positively charged DAG-lactone derivatives play a central role in determining biological activity, and that this factor contributes to the diversity of biological actions of these synthetic biomimetic ligands.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cell Membrane
/
Diglycerides
/
Lactones
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Chembiochem
Journal subject:
BIOQUIMICA
Year:
2010
Document type:
Article
Affiliation country: