Publications (2)7.89 Total impact
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Article: Membrane-surface anchoring of charged diacylglycerol-lactones correlates with biological activities.
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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.ChemBioChem 09/2010; 11(14):2003-9. · 3.94 Impact Factor -
Article: Inside Cover: Membrane-Surface Anchoring of Charged Diacylglycerol-Lactones Correlates with Biological Activities (ChemBioChem 14/2010).
ChemBioChem 09/2010; 11(14):1926. · 3.94 Impact Factor
