Long chain amines and long chain ammonium salts as novel inhibitors of dynamin GTPase activity.
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).
Hill
Timothy A
TA
Advanced Synthetic Materials Group, Chemistry Building, School Environmental and Life Sciences, The University of Newcastle, Callaghan, NSW 2308, Australia.
Odell
Luke R
LR
Quan
Annie
A
Abagyan
Ruben
R
Ferguson
Gemma
G
Robinson
Phillip J
PJ
McCluskey
Adam
A
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
D000588:Amines; D004791:Enzyme Inhibitors; D000644:Quaternary Ammonium Compounds; D012492:Salts; D034281:Dynamins