- Title
- Synthesis of dynole 34-2, dynole 2-24 and dyngo 4a for investigating dynamin GTPase
- Creator
- Robertson, Mark J.; Deane, Fiona M.; Robinson, Phillip J.; McCluskey, Adam
- Relation
- NHMRC and ARC
- Relation
- Nature Protocols Vol. 9, Issue 4, p. 851-870
- Publisher Link
- http://dx.doi.org/10.1038/nprot.2014.046
- Publisher
- Nature Publishing Group
- Resource Type
- journal article
- Date
- 2014
- Description
- Dynamin is a large GTPase with roles in membrane fission during clathrin-mediated endocytosis, in actin dynamics and in cytokinesis. Defects in dynamin have been linked to human diseases. The synthesis of a dynamin modulator toolkit comprising two different inhibitor classes is described. The first series comprises Dynole 34-2, Dynole 2-24 and the inactive control Dynole 31-2. The Dynole compounds act on the dynamin G domain, are not GTP competitive and can be synthesized in 2-3 d. Knoevenagel condensation of 1-(3(dimethylamino) propyl)-1H-indole-3-carbaldehyde (1) with cyanoamides (2 and 3) affords Dynole 31-2 and Dynole 34-2, respectively. Reductive amination of 1 with decylamine gives Dynole 2-24. The second series acts at an allosteric site in the G domain of dynamin and comprises Dyngo 4a and Dyngo Ø (inactive control). Both are synthesized in an overnight reaction via condensation of 3-hydroxy-2-naphthoic hydrazide with 2,4,5-trihydroxybenzaldehyde to afford Dyngo 4a, or with benzaldehyde to afford Dyngo Ø.
- Subject
- dynol; dyngo; clathrin-mediated endocytosis; GTPase; cytokinesis
- Identifier
- http://hdl.handle.net/1959.13/1306812
- Identifier
- uon:21262
- Identifier
- ISSN:1754-2189
- Language
- eng
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