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N-Methyl-Substituted Fluorescent DAG-Indololactone Isomers Exhibit Dramatic Differences in Membrane Interactions and Biological Activity

  1. Author:
    Gal, N.
    Kolusheva, S.
    Kedei, N.
    Telek, A.
    Naeem, T. A.
    Lewin, N. E.
    Lim, L.
    Mannan, P.
    Garfield, S. H.
    El Kazzouli, S.
    Sigano, D. M.
    Marquez, V. E.
    Blumberg, P. M.
    Jelinek, R.

  2. Author Address

    [Gal, N; Kolusheva, S; Jelinek, R] Ben Gurion Univ Negev, Dept Chem, IL-84105 Beer Sheva, Israel. [Kedei, N; Telek, A; Naeem, TA; Lewin, NE; Blumberg, PM] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA. [Lim, L; Mannan, P; Garfield, SH] NCI, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. [El Kazzouli, S; Sigano, DM; Marquez, VE] NCI, Biol Chem Lab, Ctr Canc Res, Frederick, MD 21702 USA.;Jelinek, R (reprint author), Ben Gurion Univ Negev, Dept Chem, IL-84105 Beer Sheva, Israel;razj@bgu.ac.il
    1. Year: 2011
    2. Date: Oct
  2. Journal: Chembiochem
    1. 12
    2. 15
    3. Pages: 2331-2340
  4. Type of Article: Article
  5. ISSN: 1439-4227
  1. Abstract:

    N-methyl-substituted diacylglycerol-indololactones (DAG-indololactones) are newly synthesized effectors of protein kinase C (PKC) isoforms and exhibit substantial selectivity between RasGRP3 and PKCa. We present a comprehensive analysis of membrane interactions and biological activities of several DAG-indololactones. Translocation and binding activity assays underline significant variations between the PKC translocation characteristics affected by the ligands as compared to their binding activities. In parallel, the fluorescent properties of the ligands were employed for analysis of their membrane association profiles. Specifically, we found that a slight change in the linkage to the indole ring resulted in significant differences in membrane binding and association of the DAG-indololactones with lipid bilayers. Our analysis shows that seemingly small structural modifications of the hydrophobic regions of these biomimetic PKC effectors contribute to pronounced modulation of membrane interactions of the ligands.

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External Sources

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  2. DOI: 10.1002/cbic.201100246
  3. View record in Web of Science®
  4. WOS: 000296859900016

Library Notes

  1. Fiscal Year: FY2011-2012
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