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Professor Andrew D Abell
Department of Chemistry
University of Canterbury
Private Bag 4800, Christchurch, New Zealand
Email: a.abell@chem.canterbury.ac.nz
Tel: +64-3-3642818
Fax: +64-3-3642110
Homepage: http://www.chem.canterbury.ac.nz/people/academics/ada.htm
| Research |
We are interested in the design and synthesis of peptidomimetic-based inhibitors of serine, aspartic and cysteine proteases of medicinal importance. These peptidomimetics possess reduced or modified peptidic character while maintaining many of the biologically important structural features of the parent peptide. We have developed peptidomimetics that contain a molecular switch to mask chemical reactivity. Activation on specific binding to a target protease active site releases the reactivity, resulting in specific and irreversible inactivation of the enzyme. We have a particular interest in serine proteases since the molecular details of their mechanism of action are well understood but also since an over activity of some examples has been implicated in pathological conditions including emphysema, tumor invasion and arthritis.
The conformation or shape of a peptide-based protease substrate is central to its function and as such we are also currently developing general synthetic methods to introduce rings and other conformationally rigid elements into peptidomimetic-based protease inhibitors. Current work is centred on extending our methods to the preparation of b-amino acids and peptides derived from them. This work offers the potential to produce new materials designed to carry out important chemical and biochemical transformations.
Our most recent work on protease inhibitors is centred on developing inhibitors of calpains associated with the development of human cataracts. Our goal is to develop a compound that, once incorporated into an eye drop, can be prescribed to treat cataracts.
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| Collaborations |
Professor Jim Coxon (University of Canterbury)
Dr Quentin McDonald [Q-Bit(NZ)]
Dr Jim Morton and Professor Roy Bickerstaffe (Lincoln University)
Professor Koichi Narasaka (The University of Tokyo) |
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| Publications |
Ring-deactivated hydroxyalkylpyrrole-based inhibitors of a-chymotrypsin: synthesis and mechanism of action. D. C. Martyn, A. J. Vernall, B. M. Clark, A. D. Abell, Organic & Biomolecular Chemistry, 2003, 1(12), 2103-2110.
A diastereoselective synthesis of the tetrahydropyridazinone core of 2-oxo-1,6-diazobicyclo[4.3.0]nonane-9-carboxylate-based peptidomimetics starting from (S)-phenylalanine. J. Gardiner, A. D. Abell, Tetrahedron Letters, 2003, 44(22), 4227-4230.
Synthesis of Functionalized Piperidinones. M. E. Humphries, J. Murphy, A. J. Phillips, A. D. Abell, J. Org. Chem., 2003, 68(6), 2432-2436.
Synthesis of Substituted Cyclohexenyl-Based b-Amino Acids by Ring Closing Metathesis. A. D. Abell and J. Gardiner, Org. Lett., 2002, 4, 3663-3666.
Heterocyclic-Based Peptidomimetics, A.D. Abell, Letters in Peptide Science, 2001, 8, 267-272.
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