title: Long chain amines and long chain ammonium salts as novel inhibitors of dynamin GTPase activity.
abstract: 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).
authors.affiliation: Advanced Synthetic Materials Group, Chemistry Building, School Environmental and Life Sciences, The University of Newcastle, Callaghan, NSW 2308, Australia.
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Hill
authors.forename: Luke R
authors.initials: LR
authors.lastname: Odell
authors.forename: Annie
authors.initials: A
authors.lastname: Quan
authors.forename: Ruben
authors.initials: R
authors.lastname: Abagyan
authors.forename: Gemma
authors.initials: G
authors.lastname: Ferguson
authors.forename: Phillip J
authors.initials: PJ
authors.lastname: Robinson
authors.forename: Adam
authors.initials: A
authors.lastname: McCluskey
mesh_terms: D000588:Amines / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D034281:Dynamins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D000644:Quaternary Ammonium Compounds / Q000737:chemistry* / Q000494:pharmacology; D012492:Salts / Q000737:chemistry* / Q000494:pharmacology; D012756:Sheep
chemical_list: D000588:Amines; D004791:Enzyme Inhibitors; D000644:Quaternary Ammonium Compounds; D012492:Salts; D034281:Dynamins