Jolliffe, Katrina - University of Sydney

研究领域

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.

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Liu, X., Smith, D., Jolliffe, K. (2016). Are two better than one? Comparing intermolecular and intramolecular indicator displacement assays in pyrophosphate sensors. Chemical Communications, 52(54), 8463-8466. [More Information] Larnaudie, S., Brendel, J., Jolliffe, K., Perrier, S. (2016). Cyclic peptide-polymer conjugates: Grafting-to vs grafting-from. Journal of Polymer Science, Part A: Polymer Chemistry, 54(7), 1003-1011. [More Information] Qin, L., Hartley, A., Turner, P., Elmes, R., Jolliffe, K. (2016). Macrocyclic squaramides: anion receptors with high sulfate binding affinity and selectivity in aqueous media. Chemical Science, 7(7), 4563-4572. [More Information] Veliscek-Carolan, J., Hanley, T., Jolliffe, K. (2016). The impact of structural variation in simple lanthanide binding peptides. RSC Advances, 6(79), 75336-75346. [More Information] Zwicker, V., Liu, X., Yuen, K., Jolliffe, K. (2016). Triazole-containing zinc(II)dipicolylamine-functionalised peptides as highly selective pyrophosphate sensors in physiological media. Supramolecular Chemistry, 28(1-2), 192-200. [More Information] Elmes, R., Jolliffe, K. (2015). Amino acid-based squaramides for anion recognition. Supramolecular Chemistry, 27(5-6), 321-328. [More Information] Elmes, R., Jolliffe, K. (2015). Anion recognition by cyclic peptides. Chemical Communications, 51(24), 4951-4968. [More Information] Danial, M., Perrier, S., Jolliffe, K. (2015). Effect of the amino acid composition of cyclic peptides on their self-assembly in lipid bilayers. Organic and Biomolecular Chemistry, 13(8), 2464-2473. [More Information] Veliscek-Carolan, J., Jolliffe, K., Hanley, T. (2015). Effective Am(III)/Eu(III) separations using 2,6-bis(1,2,4-triazin-3-yl)pyridine (BTP) functionalised titania particles and hierarchically porous beads. Chemical Communications, 51, 11433-11436. [More Information] Lee, S., Yuen, K., Jolliffe, K., Yoon, J. (2015). Fluorescent and colorimetric chemosensors for pyrophosphate. Chemical Society Reviews, 44(7), 1749-1762. [More Information] Ashton, T., Jolliffe, K., Pfeffer, F. (2015). Luminescent probes for the bioimaging of small anionic species in vitro and in vivo. Chemical Society Reviews, 44(14), 4547-4595. [More Information] Elmes, R., Busschaert, N., Czech, D., Gale, P., Jolliffe, K. (2015). pH switchable anion transport by an oxothiosquaramide. Chemical Communications, 51(50), 10107-10110. [More Information] Zwicker, V., Long, B., Jolliffe, K. (2015). Selective sensing of pyrophosphate in physiological media using zinc(II)dipicolylamino-functionalised peptides. Organic and Biomolecular Chemistry, 13(28), 7822-7829. [More Information] Bray, D., Clegg, J., Wenzel, M., Gloe, K., McMurtrie, J., Jolliffe, K., Gloe, K., Lindoy, L. (2015). Selective solvent extraction of silver(I) by tris-pyridyl tripodal ligands and X-ray structure of a silver(I) coordination polymer incorporating one such ligand. Australian Journal of Chemistry, 68(4), 549-554. [More Information] Wong, M., Taleski, D., Jolliffe, K. (2015). Synthesis of dichotomin A: Use of a penicillamine-derived pseudoproline to furnish native valine residues. Australian Journal of Chemistry, 68(4), 627-634. [More Information] Nortcliffe, C., Migas, L., Liu, X., Ngo, H., Jolliffe, K., Barran, P. (2015). The potential of ion mobility mass spectrometry for tuning synthetic host guest systems: A case study using novel zinc(II)dipicolylamine anion sensors. International Journal of Mass Spectrometry, 391, 62-70. [More Information] Cochrane, J., Exner, C., Jolliffe, K. (2015). Total synthesis and reassignment of the structures of the antimicrobial lipodepsipeptides circulocin gamma and delta. The Journal of Organic Chemistry, 80(9), 4491-4500. [More Information] Bray, D., Clegg, J., Jolliffe, K., Lindoy, L. (2014). Cobalt(II), iron(II), zinc(II) and palladium(II) complexes of di-topic 4'-{4-[bis(2-pyridyl)aminomethyl]phenyl}-2,2':6',2"-terpyridine. Synthetic and X-ray structural studies. CrystEngComm, 16(28), 6476-6482. [More Information] Blunden, B., Chapman, R., Danial, M., Lu, H., Jolliffe, K., Perrier, S., Stenzel, M. (2014). Drug Conjugation to Cyclic Peptide-Polymer Self-Assembling Nanotubes. Chemistry - A European Journal, 20(40), 12745-12749. [More Information] Biswas, C., Zuo, X., Chen, S., Schibeci, S., Forwood, J., Jolliffe, K., Sorrell, T., Djordjevic, J. (2014). Functional disruption of yeast metacaspase, Mca1, leads to miltefosine resistance and inability to mediate miltefosine-induced apoptotic effects. Fungal Genetics and Biology, 67, 71-81. [More Information]