- Title
- Long chain amines and long chain ammonium salts as novel inhibitors of dynamin GTPase activity
- Creator
- Hill, Timothy A.; Odell, Luke R.; Quan, Annie; Abagyan, Ruben; Ferguson, Gemma; Robinson, Phillip J.; McCluskey, Adam
- 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
- Publisher
- Elsevier Ltd.
- Resource Type
- journal article
- Date
- 2004
- 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.
- Subject
- ligand; dynamin; GTPase activity; long chain ammonium salts; long chain amines
- Identifier
- http://hdl.handle.net/1959.13/33616
- Identifier
- uon:3266
- Identifier
- ISSN:0960-894X
- Language
- eng
- Reviewed
- Hits: 7312
- Visitors: 6899
- Downloads: 0
| Thumbnail | File | Description | Size | Format |
|---|