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Professor Peter J Sadler
e-mail: p.j.sadler@ed.ac.uk tel: 0131 650 4729

Research Interests: bioinorganic chemistry, medicinal inorganic chemistry, inorganic chemical biology

Research at the interface between inorganic chemistry, biology and medicine is providing exciting new insights into biological processes, and novel ideas for the design of therapeutic agents. Our research is directed towards the design and mechanism of action of metal-based anticancer complexes, metallo-antibiotics and antiviral macrocyles. It is target-based. We are studying interactions of candidate compounds with DNA and gene expression, metal-trafficking proteins, cell receptors and signal transduction pathways. The techniques used include high field multidimensional NMR (500 - 800 MHz), chromatography, computer graphics, optical spectroscopy, chemical (and combinatorial) synthesis, X-ray crystallography, and mass spectrometry. We have strong interdisciplinary collaborations with both academia and industry.

Recent key results include the discovery of ruthenium arene anticancer complexes, the platination of DNA bases with complexes activated by visible light, the recognition of oxo-metal nanoclusters by bacterial transport proteins, an interdomain binding site for zinc on serum albumin, and the mode of interaction of macrocyclic zinc anti-HIV complexes and the CXCR4 co-receptor.

 Oxo-hafnium cluster in Fbp (Nat. Struct. Biol. 2003, 10, 297-302)Intercalation of diruthenium arene into DNA (Proc. Natl. Acad. Sci USA 2003, 100, 14623-14628)
Ru arene-nucleobase stacking (J. Am. Chem. Soc. 2002, 124, 3064-3082)Oxo-iron cluster in Fbp (Biochem. J. 2003, 376, 35-41)

SELECTED RECENT PUBLICATIONS

  1. Light-activated destruction of cancer cell nuclei by platinum diazide complexes P.J. Bednarski, R. Grünert, M. Zielzki, A. Wellner, F.S. Mackay and P.J. Sadler Chemistry & Biology 2006, 13, 61-67.
  2. Controlling ligand substitution reactions of organometallic complexes: tuning cancer cell cytotoxicity F. Wang, A. Habtemariam, E.P.L. van der Geer, R. Fernández, M. Melchart, R.J. Deeth, R. Aird, S. Guichard, F.P.A. Fabbiani, P. Lozano-Casal, I.D.H. Oswald, D.I. Jodrell, S. Parsons, P.J. Sadler Proc. Natl. Acad. Sci. USA, 2005, 102, 18269-18274.
  3. Competition between glutathione and guanine for a ruthenium(II) arene anticancer complex : detection of a sulfenato intermediate F. Wang, J. Xu, A. Habtemariam, J. Bella and P.J Sadler J. Amer. Chem. Soc.2005, 127 , 17734-17743
  4. The contrasting chemistry of cis and trans PtII diamine anticancer compounds: hydrolysis studies of picoline complexes G. McGowan, S. Parsons and P.J. Sadler Inorg. Chem. 2005, 44, 7459-7467.
  5. Organometallic chemistry, biology and medicine: ruthenium arene anticancer complexes Y.-K. Yan, M. Melchart, A. Habtemariam and P.J. Sadler Chem. Commun. 2005, 4764 - 4776
  6. G-G Base-pairing in nucleotide adducts of the anticancer drug cis-[PtCl2(NH3)(2-picoline)] and its trans isomer G. McGowan, S. Parsons and P.J. Sadler Chem. Eur. J. 2005, 11, 4396-4404.
  7. How to hide zinc in a small protein C.A. Blindauer and P.J. Sadler Acc. Chem. Res. 2005, 38, 62-69.
  8. Protein recognition of macrocycles: binding of anti-HIV metallocyclams to lysozyme. T.M. Hunter, I.W. McNae, X. Liang, J. Bella, S. Parsons, M.D. Walkinshaw, and P.J. Sadler Proc. Natl. Acad. Sci. USA 2005, 102, 2288-2292.
  9. Role of tyrosine-84 in controlling the reactivity of cysteine-34 of human albumin A.J. Stewart, C.A. Blindauer, S. Berezenko, D. Sleep, D. Tooth and P.J. Sadler FEBS J. 2005, 272, 353-362.
  10. Assembly of an oxo zirconium(IV) cluster in a protein cleft W. Zhong, D. Alexeev, I. Harvey, M. Guo, D.J.B. Hunter, H. Zhu, D.J. Campopiano and P.J. Sadler Angew. Chem. Int. Ed. 2004, 43, 5914-5918.
  11. Half-sandwich arene ruthenium(II)-enzyme complex I.W. McNae, K. Fishburne, A. Habtemariam, T.M. Hunter, M. Melchart, F. Wang, M.D. Walkinshaw and P.J. Sadler Chem. Comm. 2004, 1786-1787.
  12. Palladium(II) diamine complex reduces glutathione disulfide V. Munk and P.J. Sadler Chem. Comm. 2004, 1788-1789.
  13. Use of chelating ligands to tune the reactive site of half-sandwich ruthenium(II)-arene anticancer complexes R. Fernández, M. Melchart, A. Habtemariam, S. Parsons and P.J. Sadler Chem. Eur. J. 2004, 10, 5173-5179.
  14. Structure and dynamics of dinuclear zirconium(IV) complexes W. Zhong, J.A. Parkinson, S. Parsons, I.D.H. Oswald, R.A. Coxall and P.J. Sadler Inorg. Chem., 2004, 43, 3561-3572.
  15. Anti-viral cyclam macrocycles: rapid zinc uptake at physiological pH S.J. Paisey and P.J. Sadler Chem. Comm. 2004, 306-307.
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