Membrane-surface anchoring of charged diacylglycerol-lactones correlates with biological activities

Or Raifman, Sofiya Kolusheva, Said El Kazzouli, Dina M. Sigano, Noemi Kedei, Nancy E. Lewin, Ruben Lopez-Nicolas, Ana Ortiz-Espin, Juan C. Gomez-Fernandez, Peter M. Blumberg, Victor E. Marquez, Senena Corbalan-Garcia, Raz Jelinek

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


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 R2 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.

Original languageEnglish
Pages (from-to)2003-2009
Number of pages7
Issue number14
StatePublished - 24 Sep 2010


  • Diacylglycerol (DAG)-lactones
  • Membrane anchoring
  • Membranes
  • Protein kinases
  • Vesicles

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Organic Chemistry


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