The University of Western Australia
Adj/Prof Sue Berners-Price
Adjunct Professor
Contact details
| Address | Chemistry The University of Western Australia (M313) 35 Stirling Highway CRAWLEY WA 6009 Australia |
|---|---|
| Phone | 6488 3258 |
| Fax | 6488 1005 |
| sue.berners-price@uwa.edu.au |
Location
Room 409, Molecular and Chemical Sciences Building, Crawley campus
Biography
Royal Society Florey Fellow, (Sydney) 1987-1988
NHMRC Douglas Wright Fellow (Griffith University, Brisbane) 1992-1995
Lecturer, Senior Lecturer, Assoc. Professor (Griffith University, Brisbane) 1990-2000
NHMRC Douglas Wright Fellow (Griffith University, Brisbane) 1992-1995
Lecturer, Senior Lecturer, Assoc. Professor (Griffith University, Brisbane) 1990-2000
Key research
- Professor Sue Berners-Price was appointed to the newly established Chair in Biological Chemistry at UWA in 2001. Her teaching and research interests are in the field of Bioinorganic Chemistry and more specifically in the field of Medicinal Inorganic Chemistry. Research at the interface between inorganic chemistry, biology and medicine is providing exciting new insight into biological processes as well as novel ideas for the design of therapeutic agents involving both novel targets and novel mechanisms. Our research is directed towards the design and mechanism of action of metal-based anticancer agents. All projects involve strong interdisciplinary and some international collaboration.
Major research interests
- Bioinorganic chemistry
- Inorganic pharmacology
- NMR spectroscopy
Publications
Recent Publications
P. J. Barnard, L. E. Wedlock, M. V. Baker, S. J. Berners-Price, D. A. Joyce, B. W. Skelton, J. H. Steer. Luminescence Studies of the Intracellular Distribution of a Dinuclear Gold(I) N-Heterocyclic Carbene Complex. Angew. Chem., Int. Ed. 45, 5966-5970 (2006).
S. J. Berners-Price, L. Ronconi, P. J. Sadler. Insights into the mechanism of action of platinum anticancer drugs from multinuclear NMR spectroscopy. Prog. Nucl. Magn. Reson. Spectrosc. 49, 65-98 (2006).
M. V. Baker, P. J. Barnard, S. J. Berners-Price, S. K. Brayshaw, J. L. Hickey, B. W. Skelton, A. H. White. Cationic, linear Au(I) N-heterocyclic carbene complexes: synthesis, structure and anti-mitochondrial activity. Dalton Trans. 3708-3715 (2006).
M. V. Baker, P. J. Barnard, S. J. Berners-Price, S. K. Brayshaw, J. L. Hickey, B. W. Skelton, A. H. White. Synthesis and structural characterization of linear Au(I) N-heterocyclic carbene complexes: New analogues of the Au(I) phosphine drug Auranofin. J. Organomet. Chem. 690, 5625-5635 (2005).
J. Zhang, D. S. Thomas, M. S. Davies, S. J. Berners-Price, N. Farrell. Effects of geometric isomerism in dinuclear platinum antitumor complexes on aquation reactions in the presence of perchlorate, acetate and phosphate. J. Biol. Inorg. Chem. 10, 652-666 (2005).
S. J. Berners-Price, R. J. Bowen, M. A. Fernandes, M. Layh, W. J. Lesueur, S. Mahepal, M. M. Mtotywa, R. E. Sue, C. E. J. van Rensburg. Gold(I) and silver(I) complexes of 2,3-bis(diphenylphosphino)maleic acid: Structural studies and antitumour activity. Inorg. Chim. Acta 358, 4237-4246 (2005).
P. J. Barnard, M. V. Baker, S. J. Berners-Price, D. A. Day. Mitochondrial permeability transition induced by dinuclear gold(I)-carbene complexes: potential new antimitochondrial antitumour agents. J. Inorg. Biochem. 98, 1642-1647 (2004).
P. J. Barnard, M. V. Baker, S. J. Berners-Price, B. W. Skelton, A. H. White. Dinuclear gold(I) complexes of bridging bidentate carbene ligands: synthesis, structure and spectroscopic characterisation. Dalton Trans. 1038-1047 (2004).
S. J. Berners-Price. Targeting the mitochondrial cell death pathway with gold complexes. Chem. in Aus. 71, 10-12 (2004).
A. Hegmans, S. J. Berners-Price, M. S. Davies, D. S. Thomas, A. S. Humphreys, N. Farrell. Long Range 1,4 and 1,6-Interstrand Cross-Links Formed by a Trinuclear Platinum Complex. Minor Groove Preassociation Affects Kinetics and Mechanism of Cross-Link Formation as Well as Adduct Structure. J. Am. Chem. Soc. 126, 2166-2180 (2004).
M. S. Davies, S. J. Berners-Price, J. W. Cox, N. Farrell. The nature of the DNA template (single- versus double-stranded) affects the rate of aquation of a dinuclear Pt anticancer drug. Chem. Commun. 122-123 (2003).
S. J. Berners-Price, M. S. Davies, J. W. Cox, D. S. Thomas, N. Farrell. Competitive reactions of interstrand and intrastrand DNA-Pt adducts: A dinuclear-platinum complex preferentially forms a 1,4-interstrand cross-link rather than a 1,2 intrastrand cross-link on binding to a GG 14-mer duplex. Chem. Eur. J. 9, 713-725 (2003).
M. J. McKeage, L. Maharaj, S. J. Berners-Price. Mechanisms of cytotoxicity and antitumor activity of gold(I) phosphine complexes: the possible role of mitochondria. Coord. Chem. Rev. 232, 127-135 (2002).
M. S. Davies, D. S. Thomas, A. Hegmans, S. J. Berners-Price, N. Farrell. Kinetic and Equilibria Studies of the Aquation of the Trinuclear Platinum Phase II Anticancer Agent [{trans-PtCl(NH3)2}2{μ-trans-Pt(NH3)2(NH2(CH2)6NH2)2}]4+ (BBR3464). Inorg. Chem. 41, 1101-1109 (2002).
J. W. Cox, S. J. Berners-Price, M. S. Davies, Y. Qu, N. Farrell. Kinetic analysis of the stepwise formation of a long-range DNA interstrand cross-link by a dinuclear platinum antitumor complex: evidence for aquated intermediates and formation of both Kinetically and thermodynamically controlled conformers. J. Am. Chem. Soc. 123, 1316-1326 (2001).
M. J. McKeage, S. J. Berners-Price, P. Galettis, R. J. Bowen, W. Brouwer, L. Ding, L. Zhuang, B. C. Baguley. Role of lipophilicity in determining cellular uptake and antitumour activity of gold phosphine complexes. Cancer Chemother. Pharmacol. 46, 343-350 (2000).
M. S. Davies, S. J. Berners-Price, T. W. Hambley. Slowing of Cisplatin Aquation in the Presence of DNA but Not in the Presence of Phosphate: Improved Understanding of Sequence Selectivity and the Roles of Monoaquated and Diaquated Species in the Binding of Cisplatin to DNA. Inorg. Chem. 39, 5603-5613 (2000).
Y. Chen, J. A. Parkinson, P. Del Socorro Murdoch, Z. Guo, S. J. Berners-Price, T. Brown, P. J. Sadler. Sequence-dependent bending of DNA induced by cisplatin: NMR structures of an AT-rich 14-mer duplex. Chem. Eur. J. 6, 3636-3644 (2000).
M. S. Davies, S. J. Berners-Price, T. W. Hambley. Rates of platination of -AG- and -GA- containing double-stranded oligonucleotides: effect of chloride concentration. J. Inorg. Biochem. 79, 167-172 (2000).
M. S. Davies, J. W. Cox, S. J. Berners-Price, W. Barklage, Y. Qu, N. Farrell. Equilibrium and Kinetic Studies of the Aquation of the Dinuclear Platinum Complex [{trans-PtCl(NH3)2}2(μ-NH2(CH2)6NH2)]2+: pKa Determinations of Aqua Ligands via [1H,15N] NMR Spectroscopy. Inorg. Chem. 39, 1710-1715 (2000).
Selected Publications prior to 2000
M. S. Davies, S. J. Berners-Price, T. W. Hambley. Rates of Platination of AG and GA Containing Double-Stranded Oligonucleotides: Insights into Why Cisplatin Binds to GG and AG but Not GA Sequences in DNA. J. Am. Chem. Soc. 120, 11380-11390 (1998).
S. J. Berners-Price, P. J. Sadler. Coordination chemistry of metallodrugs: insights into biological speciation from NMR spectroscopy. Coord. Chem. Rev. 151, 1-40 (1996).
K. J. Barnham, S. J. Berners-Price, A. Corazza, P. J. Sadler. Pathways of DNA platination reactions: detection of aqua-chloro intermediates. J. Inorg. Biochem. 59, 171 (1995).
S. J. Berners-Price, T. A. Frenkiel, U. Frey, J. D. Ranford, P. J. Sadler. Hydrolysis products of cisplatin: pKa determinations via [1H,15N] NMR spectroscopy. J. Chem. Soc., Chem. Commun. 789-791 (1992).
S. J. Berners-Price, P. W. Kuchel. Reaction of cis- and trans-[PtCl2(NH3)2] (cisplatin) with reduced glutathione inside human red blood cells, studied by proton and nitrogen-15-{proton} DEPT NMR. J. Inorg. Biochem. 38, 327-345 (1990).
S. J. Berners-Price, P. J. Sadler. Phosphines and metal phosphine complexes: relationship of chemistry to anticancer and other biological activity. Structure and Bonding (Berlin, Germany) 70, 27-102 (1988).
S. J. Berners-Price, C. K. Mirabelli, R. K. Johnson, M. R. Mattern, F. L. McCabe, L. F. Faucette, C. M. Sung, S. M. Mong, P. J. Sadler, S. T. Crooke. In vivo antitumor activity and in vitro cytotoxic properties of bis[1,2-bis(diphenylphosphino)ethane]gold(I) chloride. Cancer Res. 46, 5486-5493 (1986).
S. J. Berners-Price, P. J. Sadler. Gold(I) complexes with bidentate tertiary phosphine ligands: formation of annular vs. tetrahedral chelated complexes. Inorg. Chem. 25, 3822-3827 (1986).
P. J. Barnard, L. E. Wedlock, M. V. Baker, S. J. Berners-Price, D. A. Joyce, B. W. Skelton, J. H. Steer. Luminescence Studies of the Intracellular Distribution of a Dinuclear Gold(I) N-Heterocyclic Carbene Complex. Angew. Chem., Int. Ed. 45, 5966-5970 (2006).
S. J. Berners-Price, L. Ronconi, P. J. Sadler. Insights into the mechanism of action of platinum anticancer drugs from multinuclear NMR spectroscopy. Prog. Nucl. Magn. Reson. Spectrosc. 49, 65-98 (2006).
M. V. Baker, P. J. Barnard, S. J. Berners-Price, S. K. Brayshaw, J. L. Hickey, B. W. Skelton, A. H. White. Cationic, linear Au(I) N-heterocyclic carbene complexes: synthesis, structure and anti-mitochondrial activity. Dalton Trans. 3708-3715 (2006).
M. V. Baker, P. J. Barnard, S. J. Berners-Price, S. K. Brayshaw, J. L. Hickey, B. W. Skelton, A. H. White. Synthesis and structural characterization of linear Au(I) N-heterocyclic carbene complexes: New analogues of the Au(I) phosphine drug Auranofin. J. Organomet. Chem. 690, 5625-5635 (2005).
J. Zhang, D. S. Thomas, M. S. Davies, S. J. Berners-Price, N. Farrell. Effects of geometric isomerism in dinuclear platinum antitumor complexes on aquation reactions in the presence of perchlorate, acetate and phosphate. J. Biol. Inorg. Chem. 10, 652-666 (2005).
S. J. Berners-Price, R. J. Bowen, M. A. Fernandes, M. Layh, W. J. Lesueur, S. Mahepal, M. M. Mtotywa, R. E. Sue, C. E. J. van Rensburg. Gold(I) and silver(I) complexes of 2,3-bis(diphenylphosphino)maleic acid: Structural studies and antitumour activity. Inorg. Chim. Acta 358, 4237-4246 (2005).
P. J. Barnard, M. V. Baker, S. J. Berners-Price, D. A. Day. Mitochondrial permeability transition induced by dinuclear gold(I)-carbene complexes: potential new antimitochondrial antitumour agents. J. Inorg. Biochem. 98, 1642-1647 (2004).
P. J. Barnard, M. V. Baker, S. J. Berners-Price, B. W. Skelton, A. H. White. Dinuclear gold(I) complexes of bridging bidentate carbene ligands: synthesis, structure and spectroscopic characterisation. Dalton Trans. 1038-1047 (2004).
S. J. Berners-Price. Targeting the mitochondrial cell death pathway with gold complexes. Chem. in Aus. 71, 10-12 (2004).
A. Hegmans, S. J. Berners-Price, M. S. Davies, D. S. Thomas, A. S. Humphreys, N. Farrell. Long Range 1,4 and 1,6-Interstrand Cross-Links Formed by a Trinuclear Platinum Complex. Minor Groove Preassociation Affects Kinetics and Mechanism of Cross-Link Formation as Well as Adduct Structure. J. Am. Chem. Soc. 126, 2166-2180 (2004).
M. S. Davies, S. J. Berners-Price, J. W. Cox, N. Farrell. The nature of the DNA template (single- versus double-stranded) affects the rate of aquation of a dinuclear Pt anticancer drug. Chem. Commun. 122-123 (2003).
S. J. Berners-Price, M. S. Davies, J. W. Cox, D. S. Thomas, N. Farrell. Competitive reactions of interstrand and intrastrand DNA-Pt adducts: A dinuclear-platinum complex preferentially forms a 1,4-interstrand cross-link rather than a 1,2 intrastrand cross-link on binding to a GG 14-mer duplex. Chem. Eur. J. 9, 713-725 (2003).
M. J. McKeage, L. Maharaj, S. J. Berners-Price. Mechanisms of cytotoxicity and antitumor activity of gold(I) phosphine complexes: the possible role of mitochondria. Coord. Chem. Rev. 232, 127-135 (2002).
M. S. Davies, D. S. Thomas, A. Hegmans, S. J. Berners-Price, N. Farrell. Kinetic and Equilibria Studies of the Aquation of the Trinuclear Platinum Phase II Anticancer Agent [{trans-PtCl(NH3)2}2{μ-trans-Pt(NH3)2(NH2(CH2)6NH2)2}]4+ (BBR3464). Inorg. Chem. 41, 1101-1109 (2002).
J. W. Cox, S. J. Berners-Price, M. S. Davies, Y. Qu, N. Farrell. Kinetic analysis of the stepwise formation of a long-range DNA interstrand cross-link by a dinuclear platinum antitumor complex: evidence for aquated intermediates and formation of both Kinetically and thermodynamically controlled conformers. J. Am. Chem. Soc. 123, 1316-1326 (2001).
M. J. McKeage, S. J. Berners-Price, P. Galettis, R. J. Bowen, W. Brouwer, L. Ding, L. Zhuang, B. C. Baguley. Role of lipophilicity in determining cellular uptake and antitumour activity of gold phosphine complexes. Cancer Chemother. Pharmacol. 46, 343-350 (2000).
M. S. Davies, S. J. Berners-Price, T. W. Hambley. Slowing of Cisplatin Aquation in the Presence of DNA but Not in the Presence of Phosphate: Improved Understanding of Sequence Selectivity and the Roles of Monoaquated and Diaquated Species in the Binding of Cisplatin to DNA. Inorg. Chem. 39, 5603-5613 (2000).
Y. Chen, J. A. Parkinson, P. Del Socorro Murdoch, Z. Guo, S. J. Berners-Price, T. Brown, P. J. Sadler. Sequence-dependent bending of DNA induced by cisplatin: NMR structures of an AT-rich 14-mer duplex. Chem. Eur. J. 6, 3636-3644 (2000).
M. S. Davies, S. J. Berners-Price, T. W. Hambley. Rates of platination of -AG- and -GA- containing double-stranded oligonucleotides: effect of chloride concentration. J. Inorg. Biochem. 79, 167-172 (2000).
M. S. Davies, J. W. Cox, S. J. Berners-Price, W. Barklage, Y. Qu, N. Farrell. Equilibrium and Kinetic Studies of the Aquation of the Dinuclear Platinum Complex [{trans-PtCl(NH3)2}2(μ-NH2(CH2)6NH2)]2+: pKa Determinations of Aqua Ligands via [1H,15N] NMR Spectroscopy. Inorg. Chem. 39, 1710-1715 (2000).
Selected Publications prior to 2000
M. S. Davies, S. J. Berners-Price, T. W. Hambley. Rates of Platination of AG and GA Containing Double-Stranded Oligonucleotides: Insights into Why Cisplatin Binds to GG and AG but Not GA Sequences in DNA. J. Am. Chem. Soc. 120, 11380-11390 (1998).
S. J. Berners-Price, P. J. Sadler. Coordination chemistry of metallodrugs: insights into biological speciation from NMR spectroscopy. Coord. Chem. Rev. 151, 1-40 (1996).
K. J. Barnham, S. J. Berners-Price, A. Corazza, P. J. Sadler. Pathways of DNA platination reactions: detection of aqua-chloro intermediates. J. Inorg. Biochem. 59, 171 (1995).
S. J. Berners-Price, T. A. Frenkiel, U. Frey, J. D. Ranford, P. J. Sadler. Hydrolysis products of cisplatin: pKa determinations via [1H,15N] NMR spectroscopy. J. Chem. Soc., Chem. Commun. 789-791 (1992).
S. J. Berners-Price, P. W. Kuchel. Reaction of cis- and trans-[PtCl2(NH3)2] (cisplatin) with reduced glutathione inside human red blood cells, studied by proton and nitrogen-15-{proton} DEPT NMR. J. Inorg. Biochem. 38, 327-345 (1990).
S. J. Berners-Price, P. J. Sadler. Phosphines and metal phosphine complexes: relationship of chemistry to anticancer and other biological activity. Structure and Bonding (Berlin, Germany) 70, 27-102 (1988).
S. J. Berners-Price, C. K. Mirabelli, R. K. Johnson, M. R. Mattern, F. L. McCabe, L. F. Faucette, C. M. Sung, S. M. Mong, P. J. Sadler, S. T. Crooke. In vivo antitumor activity and in vitro cytotoxic properties of bis[1,2-bis(diphenylphosphino)ethane]gold(I) chloride. Cancer Res. 46, 5486-5493 (1986).
S. J. Berners-Price, P. J. Sadler. Gold(I) complexes with bidentate tertiary phosphine ligands: formation of annular vs. tetrahedral chelated complexes. Inorg. Chem. 25, 3822-3827 (1986).
Funding received
Current research projects are encompassed under two broad areas funded by grants from the Australian Research Council.
Current projects
Application of advanced NMR techniques to investigate the biological chemistry of platinum anticancer drugs
A major contribution of our work has been the exploitation of multinuclear NMR methods for the study the chemistry of platinum anticancer drugs under conditions of biological relevance including a pioneering study of the reaction of cisplatin with glutathione inside cells. Over the past decade [1H,15N] NMR methods (developed in collaboration with Prof. Peter Sadler, Edinburgh) have provided unique insight into the molecular mechanism of action of platinum drugs including investigations of simple aquation reactions, protein binding and the kinetics and sequence selectivity of DNA binding interactions. Our current projects in this area focus on new platinum drugs under investigation.
A major current research effort focuses on the use of [1H,15N] NMR spectroscopy to probe, in detail, the DNA binding profiles of polynuclear platinum compounds related to BBR3464 (collaboration with Prof. Nick Farrell, Richmond, Virginia, USA). This trinuclear platinum compound, developed by Farrell has been evaluated in clinical trials as a new type of platinum anticancer drug with a different profile of activity to cisplatin. Our recent studies have provided important new insight into the mechanism of BBR3464. In particular, we are able to follow the stepwise formation of long-range DNA interstrand cross-links and derive kinetic parameters for each step in the pathway. A current ARC funded project addresses specific aspects of the DNA binding, metabolism and cellular uptake of both BBR3464 and second-generation analogues.
Design, synthesis and biological evaluation of gold antimitochondrial antitumour agents
In early work we identified a new class of metal phosphine antitumour agents including the Au(I) complex [Au(dppe)2]+. Clinical development of these compounds was abandoned when unacceptable levels of toxicity were identified in pre-clinical trials. However, more recent work (in collaboration with Dr. Mark McKeage, and Prof. Bruce Baguely, University of Auckland) has demonstrated that by fine-tuning the hydrophilic/hydrophobic balance of these types of compounds it is possible to eliminate the toxicity and achieve selectivity for tumour cells over normal cells. These metal-based (Au(I), Ag(I) and Cu(I)) compounds appear to act by a mechanism of action that is different to all anticancer agents currently in clinical use.
Current research efforts are directed at understanding the mechanism of action of compounds of this class, which are thought to target tumour cell mitochondria. An ARC funded project also investigates Au(I) complexes of N-heterocyclic carbenes (NHCs) as analogs of different classes of Au(I) phosphine complexes that have shown antimitochondrial activity. Several different classes of Au(I) NHC compounds are under investigation (a collaboration with Assoc. Prof. Murray Baker, UWA). A variety of different complexes have shown the ability to induce mitochondrial membrane permeabilization indicating that phosphine ligands are not essential for antimitochondrial activity. Dinuclear Au(I) NHC complexes are of particular interest as the inherent luminescent arising from the short Au-Au distances allows the investigation of the intracellular distribution in single living cancer cells using confocal fluorescence microscopy.
A major contribution of our work has been the exploitation of multinuclear NMR methods for the study the chemistry of platinum anticancer drugs under conditions of biological relevance including a pioneering study of the reaction of cisplatin with glutathione inside cells. Over the past decade [1H,15N] NMR methods (developed in collaboration with Prof. Peter Sadler, Edinburgh) have provided unique insight into the molecular mechanism of action of platinum drugs including investigations of simple aquation reactions, protein binding and the kinetics and sequence selectivity of DNA binding interactions. Our current projects in this area focus on new platinum drugs under investigation.
A major current research effort focuses on the use of [1H,15N] NMR spectroscopy to probe, in detail, the DNA binding profiles of polynuclear platinum compounds related to BBR3464 (collaboration with Prof. Nick Farrell, Richmond, Virginia, USA). This trinuclear platinum compound, developed by Farrell has been evaluated in clinical trials as a new type of platinum anticancer drug with a different profile of activity to cisplatin. Our recent studies have provided important new insight into the mechanism of BBR3464. In particular, we are able to follow the stepwise formation of long-range DNA interstrand cross-links and derive kinetic parameters for each step in the pathway. A current ARC funded project addresses specific aspects of the DNA binding, metabolism and cellular uptake of both BBR3464 and second-generation analogues.
Design, synthesis and biological evaluation of gold antimitochondrial antitumour agents
In early work we identified a new class of metal phosphine antitumour agents including the Au(I) complex [Au(dppe)2]+. Clinical development of these compounds was abandoned when unacceptable levels of toxicity were identified in pre-clinical trials. However, more recent work (in collaboration with Dr. Mark McKeage, and Prof. Bruce Baguely, University of Auckland) has demonstrated that by fine-tuning the hydrophilic/hydrophobic balance of these types of compounds it is possible to eliminate the toxicity and achieve selectivity for tumour cells over normal cells. These metal-based (Au(I), Ag(I) and Cu(I)) compounds appear to act by a mechanism of action that is different to all anticancer agents currently in clinical use.
Current research efforts are directed at understanding the mechanism of action of compounds of this class, which are thought to target tumour cell mitochondria. An ARC funded project also investigates Au(I) complexes of N-heterocyclic carbenes (NHCs) as analogs of different classes of Au(I) phosphine complexes that have shown antimitochondrial activity. Several different classes of Au(I) NHC compounds are under investigation (a collaboration with Assoc. Prof. Murray Baker, UWA). A variety of different complexes have shown the ability to induce mitochondrial membrane permeabilization indicating that phosphine ligands are not essential for antimitochondrial activity. Dinuclear Au(I) NHC complexes are of particular interest as the inherent luminescent arising from the short Au-Au distances allows the investigation of the intracellular distribution in single living cancer cells using confocal fluorescence microscopy.
Research profile
