Please use this identifier to cite or link to this item: http://hdl.handle.net/1959.13/33616

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Title
Long chain amines and long chain ammonium salts as novel inhibitors of dynamin GTPase activity
Author/Creator
Hill, Timothy A.;  Odell, Luke R.;  Quan, Annie;  Abagyan, Ruben;  Ferguson, Gemma;  Robinson, Phillip J.;  McCluskey, Adam
Institution
The University of Newcastle. Faculty of Science & Information Technology, School of Environmental and Life Science
Description
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, IC₅₀ 3.15 μM). Dynamin 1 GTPase 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.
Relation
Bioorganic & Medicinal Chemistry Letters Vol. 14, Issue 12, p. 3275-3278
Publisher Link
http://dx.doi.org/10.1016/j.bmcl.2004.03.096
Date
2004
Publisher
Elsevier Ltd.
Keyword(s)
ligand;  dynamin;  GTPase activity;  long chain ammonium salts;  long chain amines
Resource Type
journal article
Identifier
http://hdl.handle.net/1959.13/33616
Identifier
ISSN:0960-894X
Reviewed
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Subject
"Bioorganic & Medicinal Chemistry Letters"
 
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