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Academic staff: Katrina A Jolliffe

Professor

Address:

School of Chemistry, Building F11
The University of Sydney, NSW, 2006, Australia
E-mail address: K.Jolliffe@chem.usyd.edu.au
Telephone: +61-2-9351-2297
Fax: +61-2-9351-3329

Career Profile:

  • BSc(Hons), University of New South Wales, 1993
  • PhD, University of New South Wales, 1997
  • Postdoctoral Fellow, Universiteit Twente, The Netherlands 1996-1998
  • Temporary Lecturer, University of Nottingham, UK, 1998-2000
  • Research Fellow, Australian National University, 2000-2002
  • QEII Fellow, University of Sydney, 2002- 2007
  • Senior Lecturer, University of Sydney, 2007
  • Associate Professor, University of Sydney, 2008
  • Professor, University of Sydney, 2009 -

Recent Achievements:

2007: NSW and ACT Young Tall Poppy Science award

2006: Biota award for Medicinal Chemistry

2004: RACI Organic Division Lectureship for Recently Appointed Staff

Areas of interest:

  • Synthetic organic chemistry
  • Cyclic Peptide Synthesis
  • Molecular recognition and Sensing
  • Molecular self-assembly
  • Design and Synthesis of New Antifungal Agents

Details of Research:

Synthesis of Natural and Novel Cyclic Peptides

Naturally occurring cyclic peptides exhibit a wide range of biological activities and are often more resistant to enzymatic hydrolysis than their linear counterparts. Additionally, the restricted conformational flexibility of cyclic peptides allows them to present functional groups in a spatially well-defined manner and this is of use in the study and mimicry of protein folding and in the determination of the active conformations of peptides. However, the head-to-tail cyclisation of linear peptides is often a slow and low-yielding reaction. We have developed a new method for the efficient head-to-tail synthesis of small cyclic peptides and examined its use in a number of model systems. Our methodology has been employed in the synthesis of the naturally occurring cyclic peptides mahafacyclin B and axinellin A and we are currently investigating the scope of our cyclisation method and its application in the synthesis of both naturally occurring and novel cyclic peptides.

Rigidified Cyclic Peptides as Supramolecular Scaffolds

The introduction of aromatic subunits into a cyclic peptide backbone greatly reduces the conformational flexibility of these already constrained molecules and allows functional groups to be arranged in a convergent and preorganised manner suitable for binding of a guest molecule. We have used analogues of the naturally occurring Lissoclinum family of cyclic peptides, which incorporate oxazole subunits in the macrocyclic ring, to provide rigid scaffolds for the positioning of molecular receptor groups. These cyclic peptides are further rigidified by the presence of a network of bifurcated hydrogen bonds and their synthesis from amino acid building blocks allows a wide range of functional groups to be appended to the scaffold. Compounds bearing dipicolylamino zinc(II) complexes have been used to bind biologically relevant anions (e.g. pyrophosphate ions) in aqueous solution with high affinity and good selectivity. We are currently investigating how the selectivity of these receptors for target anions can be improved and looking at the attachment of alternative binding sites to the cyclic peptide scaffolds .

Development of New Antifungal Drugs

Invasive fungal infections are a serious and escalating health issue, especially in immuno-compromised hosts. Current drugs are limited in safety and/or efficacy and resistant fungi are an emerging problem. New antifungal drugs with novel modes of action are urgently needed. In collaboration with Prof. Tania Sorrell and coworkers (USyd, Westmead), we have designed and synthesised several classes of new antifungal agents. These compounds are showing great promise as antifungal drugs, with the best compounds having activity comparable to that of the current ‘gold standard’ for antifungal therapy, Amphotericin B. Current research is focussed on determining the mode of action of these compounds, which in two of the compound classes may be related to inhibition of the fungal virulence factor, phospholipase B, and in further developing classes of compounds with broad spectrum antifungal activity.

Molecular Self-Assembly

The design of molecules capable of self-assembly to form novel multicomponent supramolecular structures remains a significant challenge for synthetic chemists. Despite intense interest in the field, the assembly of synthetic structures which replicate the complexity and control apparent in the larger self-assembled biological structures is yet to be achieved. An understanding of the interactions between molecules is required to enable molecular building blocks capable of forming such structures to be designed. We are investigating the self-assembly of molecular aggregates (e.g. capsules) using both hydrogen bonding and metal-ligand interactions as the glue to hold our molecular subunits together.

Publications (2007 to 2009):

  1. Obando, D; Pantarat, N; Handke, R; Koda, Y; Widmer, F; Djordjevic, JT; Ellis, DH; Sorrell, TC and Jolliffe, KA. Synthesis, antifungal, haemolytic and cytotoxic activities of a series of bis(alkylpyridinium)alkanes. Bioorganic & Medicinal Chemistry, 17 (17), 6329-6339, 2009. DOI: 10.1016/j.bmc.2009.07.037

  2. Clegg, JK; Cochrane, JR; Sayyadi, N; Skropeta, D; Turner, P and Jolliffe, KA. Solid-state and solution-phase conformations of pseudoproline-containing dipeptides. Australian Journal of Chemistry, 62 (7), 711-719, 2009. DOI: 10.1071/CH09151

  3. Conroy, T; Jolliffe, KA and Payne, RJ. Efficient use of the Dmab protecting group: applications for the solid-phase synthesis of N-linked glycopeptides. Organic & Biomolecular Chemistry, 7 (11), 2255-2258, 2009. DOI: 10.1039/b821051a

  4. Carolan, JV; Butler, SJ and Jolliffe, KA. Selective anion binding in water with use of a zinc(II) dipicolylamino functionalized diketopiperazine scaffold. Journal of Organic Chemistry, 74 (8), 2992-2996, 2009. DOI: 10.1021/jo802555u

  5. Antonioli, B; Bray, DJ; Clegg, JK; Gloe, K; Gloe, K; Jager, A; Jolliffe, KA; Kataeva, O; Lindoy, LF; Steel, PJ; Sumby, CJ and Wenzel, M. Interaction of copper(II) and palladium(II) with linked 2,2 '-dipyridylamine derivatives: Synthetic and structural studies. Polyhedron, 27 (13), 2889-2898, 2008. DOI: 10.1016/j.poly.2008.06.036

  6. Beves, JE; Bray, DJ; Clegg, JK; Constable, EC; Housecroft, CE; Jolliffe, KA; Kepert, CJ; Lindoy, LF; Neuburger, M; Price, DJ; Schaffner, S and Schaper, F. 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+. Inorganica Chimica Acta, 361 (9-10), 2582-2590, 2008. DOI: 10.1016/j.ica.2007.10.040

  7. Clegg, JK; Jolliffe, KA; Lindoy, LF and Meehan, GV. Metallo-supramolecular assemblies incorporating 1,3-and 1,4-aryl linked bis-beta-diketones - Some recent studies. Polish Journal of Chemistry, 82 (6), 1131-1144, 2008.

  8. Bray, DJ; Antonioli, B; Clegg, JK; Gloe, K; Gloe, K; Jolliffe, KA; Lindoy, LF; Wei, G and Wenzel, M. Assembly of a trinuclear metallo-capsule from a tripodal tris(beta-diketone) derivative and copper(II). Dalton Transactions, (13), 1683-1685, 2008. DOI: 10.1039/b717685f

  9. Clegg, JK; Bray, DJ; Gloe, K; Gloe, K; Jolliffe, KA; Lawrance, GA; Lindoy, LF; Meehane, GV and Wenzelb, M. Synthetic, structural, electrochemical and solvent extraction studies of neutral trinuclear Co(II), Ni(II), Cu(II) and Zn(II) metallocycles and tetrahedral tetranuclear Fe(III) species incorporating 1,4-aryl-linked bis-beta-diketonato ligands. Dalton Transactions, (10), 1331-1340, 2008. DOI: 10.1039/b716653b

  10. Bray, DJ; Clegg, JK; Jolliffe, KA; Lindoy, LF and Wei, G. Synthesis and co-crystallisation behaviour of copper(II) complexes of two isomeric p-tolyl-terpyridines. Journal of Coordination Chemistry, 61 (1), 3-13, 2008. DOI: 10.1080/00958970701700987

  11. Obando, D; Widmer, F; Wright, LC; Sorrell, TC and Jolliffe, KA. Synthesis, antifungal and antimicrobial activity of alkylphospholipids. Bioorganic & Medicinal Chemistry, 15 (15), 5158-5165, 2007. DOI: 10.1016/j.bmc.2007.05.028

  12. Tong, ZS; Widmer, F; Sorrell, TC; Guse, Z; Jolliffe, KA; Halliday, C; Lee, OC; Kong, FR; Wright, LC and Chen, SCA. In vitro activities of miltefosine and two novel antifungal biscationic salts against a panel of 77 dermatophytes. Antimicrobial Agents and Chemotherapy, 51 (6), 2219-2222, 2007. DOI: 10.1128/AAC.01382-06

  13. Ng, CKL; Singhal, V; Widmer, F; Wright, LC; Sorrell, TC and Jolliffe, KA. Synthesis, antifungal and haemolytic activity of a series of bis(pyridinium)alkanes. Bioorganic & Medicinal Chemistry, 15 (10), 3422-3429, 2007. DOI: 10.1016/j.bmc.2007.03.018

  14. Clegg, JK; Bray, DJ; Gloe, K; Gloe, K; Hayter, MJ; Jolliffe, KA; Lawrance, GA; Meehan, GV; McMurtrie, JC; Lindoy, LF and Wenzel, M. Neutral (bis-beta-diketonato) iron(III), cobalt(II), nickel(II), copper(II) and zinc(II) metallocycles: structural, electrochemical and solvent extraction studies. Dalton Transactions, (17), 1719-1730, 2007. DOI: 10.1039/b701575e

  15. Bray, DJ; Jolliffe, KA; Lindoy, LF and McMurtrie, JC. Tris-beta-diketones and related keto derivatives for use as building blocks in supramolecular chemistry. Tetrahedron, 63 (9), 1953-1958, 2007. DOI: 10.1016/j.tet.2006.12.071

  16. Antonioli, B; Bray, DJ; Clegg, JK; Jolliffe, KA; Gloe, K; Gloe, K and Lindoy, LF. Proton and anion control of framework complexity in copper(II) complex structures derived from 2-(hydroxymethyl)pyridine. Polyhedron, 26 (3), 673-678, 2007. DOI: 10.1016/j.poly.2006.08.031

  17. Banister, SD; Clegg, JK; Coster, MJ; Jolliffe, KA and Kassiou, M. (1R,2S,3R,6S,7R,8S)-Tricyclo[6.2.1.02,7]-undeca-4,9-diene-3,6-diol. Acta Crystallographica Section E-Structure Reports Online, E63, o92-o93, 2007. DOI: 10.1107/S1600536806051002
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