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Professor Paul F Alewood*
Institute for Molecular Bioscience
University of Queensland
Brisbane, Qld 4072
Email: P.Alewood@imb.uq.edu.au
Tel: +61-7-3346-2982
Fax: +61-7-3346-2101
Homepage: http://www.imb.uq.edu.au/index.html?id=11694

Currently we are working o new synthetic methods to establish accesss to small proteases (<250 residues). The strategy involves the regioselective ligation of smaller protease segments. This has the advantages of further probing the structure-activity relationships of the enzyme through the incorporation of non-coded amino acids and organic constructs. These may also contain useful tags and fluorescent probes that can be incorporated into the enzyme(s) at precise locations.
In my current ARC funded HIV-1 Protease project I am aiming to design and prepare by total chemical synthesis an HIV-1 PR-derived enzyme containing an artificial catalytic apparatus with systematically ‘tunable’ properties to investigate the electronic effects on the mechanism of peptide hydrolysis and understand the molecular basis of enzyme catalysis.
Professor Stephen Kent, University of Chicago
Jenny Martin (UQ)
David Fairlie (UQ)
Total Chemical Synthesis of Proteins: Evolution of Solid Phase Synthetic Methods illustrated by the Total Chemical Syntheses of the HIV-1 Protease. SBH Kent, D Alewood, P Alewood, M Baca, A Jones and M Schnollzer. Innovation and Perspectives in Solid Phase Synthesis (Roger Epton, Ed) Intercept Limited, Andover, 1992, pp 1-22

Structural engineering of the HIV-1 protease molecule with a b- turn mimic of fixed geometry. M Baca, PF Alewood and S Kent. Protein Science, 2, 1085-91, 1993.

Kinetic Properties of HIV-1 Protease produced by total chemical synthesis. D Bergman, D Alewood, PF Alewood, J Andrews, RI Brinkworth, D Englebretsen and SBH Kent. Letters in Peptide Science, 2, 99-107 (1995).

A Novel Thioether Linker: Chemical Synthesis of a HIV-1 Protease Analogue by Thioether Ligation. Darren R. Englebretsen, Bronwyn G. Garnham, Douglas Bergman and Paul F. Alewood. Tetrahedron Letters, 36 (48) 8871-8874, 1995.

Molecular Recognition of Macrocyclic Peptidomimetic HIV-1 Protease inhibitors. J Martin, J Begun, A Schindeler, W Wickramasinghe, D Alewood, PF Alewood, D Bergman, R Brinkworth, G Abbenante, D March, R Reid and DF Fairlie. Biochemistry, 38 (25) 7978-7988, 1999.

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