Please use this identifier to cite or link to this item: http://hdl.handle.net/1959.13/917168
- Title
- Azido and diazarinyl analogues of bis-tyrphostin as asymmetrical inhibitors of dynamin GTPase
- Author/Creator
-
Odell, Luke R.;
Chau, Ngoc;
Mariana, Anna;
Graham, Mark E.;
Robinson, Phillip J.;
McCluskey, Adam
- Institution
- The University of Newcastle. Faculty of Science & Information Technology, School of Environmental and Life Sciences
- Description
- Two azidobenzyl amide (4 and 23) and one 3-trifluoromethyl-3H-diazirin-3-ylphenyl (24) analogues of bis-tyrphostin (1, Bis-T) were synthesised as potential photoaffinity labels for the elucidation of the binding site of compound 1 in dynamin I. Of the two azidobenzyl amide analogues (4 and 23), the terminally substituted 23 retained dynamin I GTPase inhibition (IC₅₀= 6.4±2.8 μm) whilst 4, which was substituted on the central carbon of the amide linker, displayed no activity. Analogue 24 also retained inhibitory activity (IC₅₀=36±9 μm). Photoaffinity labelling experiments did not unequivocally elucidate the binding pocket of compound 1. However, compounds 23 and 24 represent the first asymmetrically substituted Bis-T analogues to retain dynamin inhibitory activity, providing a new direction for analogue synthesis.
- Relation
- Chemmedchem Vol. 4, Issue 7, p. 1182-1188
- Publisher Link
- http://dx.doi.org/10.1002/cmdc.200900054
- Date
- 2009
- Publisher
- Wiley
- Keyword(s)
-
bis tyrphostin;
dynamin GTPase I;
inhibitors;
photoaffinity;
synthesis
- Resource Type
- journal article
- Identifier
- http://hdl.handle.net/1959.13/917168
- Identifier
- ISSN:1860-7179
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