Senior Lecturer
CONTACT DETAILS:
Address: Bio21 Institute, School of
Chemistry, University of Melbourne, Parkville, VIC 3010 Australia
Room: Bio 21 Inst. 502
Email: chutton@unimelb.edu.au
Teaching responsibilities
Field of expertise
Bioorganic Chemistry
Synthesis of Biologically Active Cyclic Peptides
In recent years several complex cyclic peptides with remarkable biological activities have gained prominence in clinical medicine, such as the antibiotic vancomycin which remains the antibiotic of last resort for the treatment of multi-drug resistant bacterial infections. Current efforts are directed towards the synthesis of the ustiloxin/phomopsin family - a group of anti-tumour cyclic peptides with high potency against human breast and lung cancer cell lines; and the pneumocandins and microsclerodermins -- antifungal agents being used in the treatment of HIV-related fungal infections. New methods for the stereocontrolled synthesis of the highly functionalised amino acid residues present in these peptides, and the assembly of the amino acid components into the final cyclic peptides, are being investigated.
Inhibitors of Enzymes in the Lysine Biosynthetic Pathway
Recent emergence of bacterial strains resistant to our antibiotics of last resort´ highlights the need for continual development of new antibacterial agents. Compounds which inhibit the biosynthesis of the amino acid lysine are being designed in order to develop a new class of antibiotics which exert their biological effect through suppression of bacterial cell wall and protein synthesis. Lysine is one of the 'essential amino acids' which must be obtained through our diet, suggesting that antibiotics of this type should also possess low toxicity to mammals. Current studies are focussed on the design and synthesis of inhibitors of DHDP synthase, the enzyme which catalyses the first committed step in lysine biosynthesis, as well as elucidation of the enzymatic reaction mechanism of DHDP synthase.
Cross-linked Tyrosine Residues in Peptides and Proteins
In recent years the importance of cross-linked tyrosine residues in conferring specific functional roles to peptides and proteins has come to light. Examples include the modification of catalytic active sites of enzymes, oxidative cross-linking processes involved in aging and disease, and the conformational effects of these cross-links in biologically active cyclic peptides. A novel method for the preparation of a number of crosslinked tyrosine derivatives is currently being developed, using tyrosine-boronic acids as substrates in various coupling strategies.
For further information view the Hutton research group page.
Selected Publications:
- Turner, J. J.; Gerrard, J. A. and Hutton, C. A., Bioorg. Med. Chem., 2005, 13, 2133-2140.
- Turner, J. J.; Healy, J. P.; Dobson, R. C. J.; Gerrard, J. A. and Hutton, C. A., Bioorg. Med. Chem. Lett., 2005, 15, 995-998.
- Pennington, T. E.; Kardiman, C. and Hutton, C. A., Tetrahedron Lett., 2004, 45, 6657-6660.
- Hunter, L. and Hutton, C. A., Aust. J. Chem., 2003, 56, 1095-1098.
- Hutton, C. A. and Skaff, O. Tetrahedron Lett., 2003, 44, 4895-4898.
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