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Bioorg Med Chem Lett. 2004 Jun 21;14(12):3275-8.

Long chain amines and long chain ammonium salts as novel inhibitors of dynamin GTPase activity.

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  • 1Advanced Synthetic Materials Group, Chemistry Building, School Environmental and Life Sciences, The University of Newcastle, Callaghan, NSW 2308, Australia.


We examined a number of ligands with the view of inhibiting the GTPase activity of dynamin. Dynamin contains a pleckstrin homology (PH) domain that interacts with lipids. We report a series of simple lipid-like molecules that display moderate inhibitory activity. Inhibitory activity is linked to chain length and quaternarization of the terminal amine. A change in the counterion, Cl versus Br or I, had little effect on potency. However, introduction of a hydrophobic collar proximal to the charged site was beneficial to dynamin GTPase inhibitory action. The most potent compound was myristoyl trimethyl ammonium bromide (MTMAB, IC(50) 3.15 microM).

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