International Protease Network

Institute for Molecular Bioscience
University of Queensland
Brisbane, Qld 4072
Email: r.reid@imb.uq.edu.au
Tel: +61-7-3346-2991
Fax: +61-7-3346-2101 or 2103
Homepage: http://www.imb.uq.edu.au

Research

We have an ongoing interest in the design and chemical synthesis of protease inhibitors intended for use as human therapeutics. We have expertise with receptor based drug design methods that employ X-ray crystal structures of a target protease and sophisticated computational techniques to discover new protease inhibitors, or enhance the potency and selectivity of known compounds. Primary expertise is Organic Chemistry, hence the preparation of any conceivable compound is considered absolutely achievable in our own laboratory. Novel approaches to inhibitor design are used to generate molecules that are rigidly constrained to the conformation recognised by the protease (extended, or beta strands).

Collaborations

David P. Fairlie (Group Leader, Chemical Biology)
Jennifer L. Martin (Crystallographer, X-ray and Synchrotron)
Joel D. A. Tyndall(Molecular Modeling and Computational Chemistry)

Publications

Reid, R. C.; Pattenden, L. K.; Tyndall, J. D. A.; Martin, J. L.; Walsh, T.; Fairlie, D. P. Countering Cooperative Effects in Protease Inhibitors Using Constrained b-Strand-Mimicking Templates in Focused Combinatorial Libraries. J. Med. Chem. 2004, 47, In Press.

Reid, R. C.; Kelso, M. J.; Scanlon, M. J.; Fairlie, D. P. Conformationally Constrained Macrocycles That Mimic Tripeptide b-Strands in Water and Aprotic Solvents. Journal of the American Chemical Society 2002, 124, 5673-5683.

Reid, R. C.; March, D. R.; Dooley, M. J.; Bergman, D. A.; Abbenante, G.; Fairlie, D. P. A Novel Bicyclic Enzyme Inhibitor as a Consensus Peptido-Mimetic for the Receptor-Bound Conformations of Twelve Peptidic Inhibitors of HIV-1 Protease. J. Am. Chem. Soc. 1996, 118, 8511-8517.

Tyndall, J. D. A.; Reid, R. C.; Tyssen, D. P.; Jardine, D. K.; Todd, B.; Passmore, M.; March, D. R.; Pattenden, L. K.; Bergman, D. A.; Alewood, D.; Hu, S.-H.; Alewood, P. F.; Birch, C. J.; Martin, J. L.; Fairlie, D. P. Synthesis, stability, antiviral activity, and protease-bound structures of substrate-mimicking constrained macrocyclic inhibitors of HIV-1 protease. J. Med. Chem. 2000, 43, 3495-3504.

Martin, J. L.; Begun, J.; Schindeler, A.; Wickramasinghe, W. A.; Alewood, D.; Alewood, P. F.; Bergman, D. A.; Brinkworth, R. I.; Abbenante, G.; March, D. R.; Reid, R. C.; Fairlie, D. P. Molecular recognition of macrocyclic peptidomimetic inhibitors by HIV-1 protease. Biochemistry 1999, 38, 7978-7988.