Professor Katrina Jolliffe

Antifungal Drug Development Group

• Research Interests
• Publications
• Contact Details

Kate Jolliffe is a Professor in the School of Chemistry at the University of Sydney.

Kate is a graduate of the University of New South Wales, where she completed her PhD in 1997. She then held a postdoctoral position at the University of Twente in the Netherlands before taking up a lectureship at the University of Nottingham in 1998.

In March 2000, Kate returned to Australia as an Institute of Advanced Studies Research Fellow in the Research School of Chemistry at the Australian National University.

In February 2002 she moved to the School of Chemistry at The University of Sydney to take up an ARC QEII Research Fellowship and in February 2007 took up a research and teaching position at the same institution.

Research Interests

Research in my group is directed towards the design and synthesis of small molecules for use in biological and medical applications. Projects include the development of novel antifungal agents, the design and evaluation of molecular receptors for biologically important anions and the synthesis of small cyclic peptides, both naturally occurring and novel.

New Antifungal Agents

We are currently investigating a number of compound classes for their antifungal activity. With an increase in the occurrence of fungal infections and the emergence of resistant fungi, new antifungal agents with a novel mode of action are urgently required. Virulence factors and biochemical and signal transduction pathways unique to fungi are potential targets for anti-fungal drug development. To date, our studies have focussed on the development of inhibitors for the secreted enzyme, phospholipase B (PLB1), which is a known fungal virulence factor.

Compounds from four different structural classes have been synthesised and the antifungal activity of these compounds, together with their ability to inhibit fungal PLB1, has been investigated to establish structure-activity relationships. We have found a number of compounds that exhibit strong antifungal activity, comparable with that of some currently used antifungal agents. For one class of compounds, antifungal activity correlated with PLB1 inhibition, suggesting that this is a possible mode of action for these compounds. We are currently refining the compound structures to prepare compounds with improved antifungal activity and to assist in determining their antifungal mode of action.

Synthetic Molecular Receptors

Small molecules capable of binding selectively to molecular guests and signalling their presence are of great interest as sensors for a variety of applications. We are interested in developing such sensors capable of binding molecules of biological relevance under physiological conditions for use in biomedical applications. For example, pyrophosphate ions (PPi) are produced as a byproduct in many enzymatic reactions, so the ability to directly detect PPi in the presence of structurally similar enzyme substrate molecules (e.g. ATP or pyrophosphate esters) would be a useful method of following the progress of such reactions. We have recently developed a receptor based on a backbone modified cyclic peptide that is capable of sensing PPi with a selectivity of 2 orders of magnitude over ATP. Current work is focussed on improving the selectivity of the receptors and developing sensors for other molecules of interest.

In a separate study (in collaboration with Prof. B. D. Smith, University of Notre Dame, USA), we have developed small molecules, bearing fluorescent tags, that are capable of selectively recognising phosphatidylserine in the outer leaflet of cell membranes. These molecules are therefore able to selectively detect apoptotic cells and are compatible with current flow cytometry equipment. They have several advantages over the currently used Annexin-V assay, including cost, ability to assay without added Ca2+ and fast binding kinetics.

Cyclic Peptides

The synthesis of cyclic peptides and derivatives is of significant interest, due to their potential applications in a range of areas spanning both chemistry and biology. Naturally occurring cyclic peptides exhibit a wide range of biological activities and a particular advantage of their cyclic structure is a higher resistance to enzymatic degradation than their linear counterparts. Cyclisation of a linear peptide restricts the conformational flexibility of the molecule and can be used to lock a peptide into its bioactive conformation, enhancing biological activity.

The synthesis of small cyclic peptides is often a slow and low-yielding reaction, strongly dependant upon peptide sequence. We have developed methodology to improve the yields of cyclisation for small peptides (4-9 amino acids) and are now applying this to the synthesis of cyclic peptides with biological activity. To date we have prepared a naturally occurring cyclic peptide with antimalarial activity and the cyclic peptide core of a naturally occurring antifungal compound.

In collaboration with Dr L. Rendina (Chemistry, USyd) we are investigating the attachment of RGD cyclic peptides, capable of selectively targeting cancer cells, to boron containing molecules. This will allow selective delivery of the boron to cancer cells for use in Boron Neutron Capture Therapy.

Publications

- 2009 - 2008 - 2007 - 2006 - 2005 - 2004 -

2009

• Selective Anion Binding in Water using a Zinc(II)Dipicolylamino Functionalised Diketopiperazine Scaffold. J. Veliscek-Carolan, S. J. Butler and K. A. Jolliffe, J. Org. Chem., 2009, 74, 2992-2996. [Abstract]

2008

• Interaction of Copper(II) and palladium(II) with linked 2,2'-dipyridylamine derivatives. Synthetic and structural studies. B. Antonioli, D. J. Bray, J. K. Clegg, K. Gloe, K. Gloe, A. Jäger, K. A. Jolliffe, O. Kateva, L. F. Lindoy, P. J. Steel, C. J. Sumby, M. Wenzel, Polyhedron, 2008, 13, 2889-2898.
• Metallo-Supramolecular Assemblies Incorporating 1,3- and 1,4-Aryl Linked Bis-b-Diketones – Some Recent Studies. Jack K. Clegg, Katrina A. Jolliffe, Leonard F. Lindoy and George V. Meehan, Polish J. Chem., 2008, 82, 1131–1144. [Abstract]
• Assembly of a trinuclear metallo-capsule from a tripodal tris(b-diketone) derivative and copper (II). D. J. Bray, B. Antonioli, J. K. Clegg, K. Gloe, K. Gloe, K. A. Jolliffe, L. F. Lindoy, G. Wei and M. Wenzel, Dalton Trans., 2008, 1683-1685.
• Synthetic, structural, electrochemical and solvent extraction studies of neutral trinuclear cobalt(II), nickel(II), copper(II) and zinc(II) metallocycles and tetrahedral tetranuclear iron(III) species incorporating 1,4-aryl-linked bis-b-diketonato ligands. J. K. Clegg, D. J. Bray, K. Gloe, K. Gloe, K. A. Jolliffe, G. A. Lawrance, L. F. Lindoy, G. V. Meehan and M. Wenzel, Dalton Trans., 2008, 1331-1340. [Abstract]
• Expanding the 4,4’-bipyridine ligand: structural variation in {M(pytpy)2}2+ complexes (pytpy = 4’-(4-pyridyl)-2,2’:6’,2”-terpyridine, M = Fe, Ni, Ru) and assembly of the hydrogen-bonded, one-dimensional polymer {[Ru(pytpy)(Hpytpy)]}n3n+, J. E. Beves, D. J. Bray, J. K. Clegg, E. C. Constable, C. E. Housecroft, K. A. Jolliffe, C. J. Kepert, L. F. Lindoy, M. Neuburger, D. J. Price, S. Chaffner and F. Schaper, Inorganica Chimica Acta., 2008, 11, 805-808.
• Synthesis and Co-Crystallisation Behaviour of Copper(II) Complexes of Two Isomeric p-Tolyl-Terpyridines, D. J. Bray, J. K. Clegg, K. A. Jolliffe, L. F. Lindoy and G. Wei, J. Coord. Chem., 2008, 61, 3-13.

2007

• Synthesis, Antifungal and Antibacterial Activity of Alkylphospholipids. D. Obando, F. Widmer, L. C. Wright, T. C. Sorrell and K. A. Jolliffe, Bioorg. Med. Chem., 2007, 15, 5158-5165. [Abstract]
• Synthesis, Antifungal and Hemolytic Activity of a Series of Bis(pyridinium)alkanes. C. K. L. Ng, V. Singhal, F. Widmer, L. C. Wright, T. C. Sorrell and K. A. Jolliffe, Bioorg. Med. Chem., 2007, 15, 3422-3429. [Abstract]
• In-vitro activity of miltefosine and two novel antifungal bis-cationic salts against a panel of 77 dermatophytes. Z. Tong, F. Widmer, T. C. Sorrell, Z. Guse, K. A. Jolliffe, C. Halliday, O. C. Lee, F. Kong, L. C. Wright and S. C. A. Chen, Antimicrob. Agents Chemother., 2007, 51, 2219-2222. [Abstract]
• Tris b-diketones and related keto derivatives for use as building blocks in supramolecular chemistry. D. J. Bray, K. A. Jolliffe, L. F. Lindoy and J. C. McMurtrie, Tetrahedron, 2007, 63 , 1953-1958.

2006

• Preparation of the Central Tryptophan Moiety of the Celogentin/Moroidin Family of Anti-mitotic Cyclic Peptides, A. K. L. Yuen, K. A. Jolliffe and C. A. Hutton, Aust. J. Chem, 2006, 59, 819-826.
• Selective Recognition of Pyrophosphate in Water Using a Backbone Modified Cyclic Peptide Receptor. M. J. McDonough, A. J. Reynolds, W. Y. G. Lee and K. A. Jolliffe, Chem Commun., 2006, 2971-2973. [Abstract]
• Synthetic Peptides with Selective Affinity for Apoptotic Cells. K. M. DiVittorio, J. R. Johnson, E. Johansson, A. J. Reynolds, K. A. Jolliffe and B. D. Smith, Org. Biomol. Chem., 2006, 4, 1966-1976. [Abstract]
• Correlation of Antifungal Activity with Fungal Phospholipase Inhibition using a Series of Bisquaternary Ammonium Salts. C. K. L. Ng, D. Obando, F. Widmer, L. Wright, T. C. Sorrell and K. A. Jolliffe, J. Med. Chem., 2006, 49, 811-816. [Abstract]

2005

• N,O-Isopropylidenated Threonines as Tools for Peptide Cyclisation: Application to the Total Synthesis of Mahafacyclin B. N. Sayyadi, D. Skropeta and K. A. Jolliffe, Org. Lett., 2005, 7, 5497-5499.
• Synthesis of the Side-Chain Cross-Linked Tyrosine Oligomers Dityrosine, Trityrosine, and Pulcherosine. O. Skaff, K. A. Jolliffe and C. A. Hutton, J. Org. Chem., 2005, 70, 7353-7363.
• Backbone Modified Cyclic Peptides: New Scaffolds for Supramolecular Chemistry. K. A. Jolliffe, Supramol. Chem. 2005, 17, 81-86.

2004

• Pseudo-prolines as Removable Turn Inducers: Tools for the Cyclisation of Small Peptides. D. Skropeta, K. A. Jolliffe, P. Turner, J. Org. Chem., 2004, 69, 8804-8809
• Synthesis of the Sialic Acid (-)-KDN and Certain Epimers from (-)-3-Dehydroshikimic Acid or (-)-Quinic Acid. M. G. Banwell, N. L. Hungerford, K. A. Jolliffe, Org. Lett., 2004, 6, 2737-2740.
• Self-Assembly Directed by NH-O Hydrogen Bonding. K. A. Jolliffe and L. F. Lindoy, Encyclopedia of Nanoscience and Nanotechnology, Marcel Dekker, Eds. J. A. Schwarz, C. Contescu and K. Putyera, New York, 2004, 3399-3413.

Contact Details

T +61 2 9351 2297

F +61 2 9351 3329

E K.Jolliffe@chem.usyd.edu.au