长链胺和长链铵盐作为发动蛋白GTP酶活性的新型抑制剂。
Long chain amines and long chain ammonium salts as novel inhibitors of dynamin GTPase activity.
作者信息
Hill Timothy A, Odell Luke R, Quan Annie, Abagyan Ruben, Ferguson Gemma, Robinson Phillip J, McCluskey Adam
机构信息
Advanced Synthetic Materials Group, Chemistry Building, School Environmental and Life Sciences, The University of Newcastle, Callaghan, NSW 2308, Australia.
出版信息
Bioorg Med Chem Lett. 2004 Jun 21;14(12):3275-8. doi: 10.1016/j.bmcl.2004.03.096.
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).
我们研究了多种配体，旨在抑制发动蛋白的GTP酶活性。发动蛋白含有一个与脂质相互作用的普列克底物蛋白同源（PH）结构域。我们报告了一系列具有中等抑制活性的简单类脂分子。抑制活性与链长和末端胺的季铵化有关。抗衡离子从Cl变为Br或I对效力影响不大。然而，在带电位点附近引入一个疏水环对发动蛋白GTP酶抑制作用有益。最有效的化合物是肉豆蔻酰三甲基溴化铵（MTMAB，IC(50) 3.15 microM）。
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