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School of Pharmacy and Pharmaceutical Sciences

Professor Ken Douglas PhD, MA,

Photograph of Ken Douglas

Honorary Professor

 

Memberships of Committees and Professional Bodies

  • Section Editor for Biochimica Biophysica Acta, Gene Structure and Expression and serves / has served on the editorial boards of several scientific journals
  • Member of the Biochemical Society (London)
  • Member of the Society for Drug Research
  • Member of the British Association for Cancer Research
  • Member of the European Association for Cancer Research
  • Member of the United Kingdom Association of Pharmaceutical Scientists

Research

His research takes a multidisciplinary approach to rational development of new drug leads, primarily in parasitic diseases and cancer, and in the application of modern medicinal chemistry approaches to the rational basis of novel molecular diagnostics design.  The rational drug design process that his lab applies in parasitology specifically targets trypanosomiasis and leishmaniasis, as well as malaria.  More recently his lab has been applying structure-based molecular design principles to develop the field of rational design of molecular diagnostics.

In his laboratory both proteins and nucleic acids are used as targets for lead ligand design, followed by synthesis and evaluation for target inhibition/binding.  Expertise in his group includes protein homology modelling, novel ligand design and synthesis, enzymology, fast reaction techniques, DNA and RNA chemistry and high-field NMR spectroscopy of novel DNA structures and of DNA: ligand complexes. 

He has published some 200 refereed papers plus a 5 patent filings in these areas.  He has major, productive links with leading international research groups in Japan (Universities of Kyoto, Toyohashi and Saitama), Europe (Universite Paul-Sabatier, France, University of Lisbon) and Russia (Institute of Bioorganic Chemistry, Novosibirsk) and SE Asia (Mahidol University, Thailand and Dhaka University, Bangladesh).  He has worked closely with the UK and European Pharma and Diagnostics industry, and has just completed a BBSRC/DTI/LINK grant with industry in the field of novel fluorescence approaches to molecular diagnostics.  A related programme on new approaches to photo-electronic method development, funded by EPSRC, is run jointly with Dr. Elena Bichenkova of the School of Pharmacy and Drs B. Coe and S. Faulkner in the Department of Chemistry.  In addition, he has been contributing to a new DTI LINK with LGC plc in the field of fluorescence detection of nucleic acids along with Drs. R. Bryce and E.V. Bichenkova.  In addition, his lab is developing a novel approach to re-engineering the widely used Green Fluorescent Protein to make it suitable for chemical manipulation and subsequent use in cellular studies (supported by BBSRC and involving a close laboratory-level collaboration with the group of Dr Miho Suzuki at Saitama University in Japan). 

Integrating these areas with other academics’ active research themes in the School of Pharmacy and Pharmaceutical sciences, he has led a team of colleagues that has been supported by the Wolfson Foundation to establish in 2003 a Centre in Rational Structure-Based Design of Molecular Diagnostics, certainly the first of its kind in the UK and probably in the world.  

 

Biography

Ken Douglas is presently the Director of the Wolfson Centre for Rational Design of Molecular Diagnostics (the Centre integrates the research of 7 academic teams from across the school of Pharmacy and of Biology).  In 1987 he was appointed Professor of Medicinal Chemistry in the University of Manchester, and has served since then as Head of the Drug Action and Design Group (a group of 12 academics each with a research programme in the title area).  In the period 1978-87 he was Lecturer in Biological Chemistry at the University of Essex.  From1975-78 he was Assistant Professor and then Associate Professor (in 1978) in the Department of Chemistry and Biochemistry at, Duquesne University, Pittsburgh in the USA.  Prior to that (1973-75) he was a Postdoctoral Research Fellow in the University of Chicago in the USA with Professor E T Kaiser.

 

Qualifications

  • BA (Hons) Chemistry - Balliol College, University of Oxford
  • 1973 - PhD Physical Organic Chemistry - University of Kent
  • 1973 - MA Chemistry - University of Oxford
  • 2007 - present, Member of Health Research Board of Ireland, Research Award Panel in Pharmacology and Physiology
  • 2004 - present, Member of RAE 2008 Sub-panel for Pharmacy
  • 2002 - Royal Society of Chemistry’s industrially sponsored Silver Medal for Medicinal Chemistry
  • 1983 - Matsumae International Medal and Fellowship to Japan 
  • 1976 - Pittsburgh Spectroscopic Society’s College Award (co-winner)
  • 1966 - Sir Hans Sloane Medal 
  • 1991-1992 - Visiting Professor at Université Paul-Sabatier, Toulouse, France
  • 1983 - Honorary Professor at Nagasaki University, Japan
  • 1978 - Visiting Professor at Université de Paris-Sud, Orsay, France
 

Selected publications

2009

  • Mitchell F, Frank F, Marks G, Suzuki M, Douglas KT, Bryce RA. (2009). Molecular dynamics study of chemically engineered green fluorescent protein mutants: Comparison of intramolecular fluorescence resonance energy transfer rate. Proteins, 75( 1), 28-39. eScholarID:1d18711 | DOI:10.1002/prot.22218
  • Neres, J, Brewer, M, Ratier, L, Botti, H, Buschiazzo, A, Edwards, P, Mortenson, P, Charlton, M, Alzari, P, Frasch, A, Bryce, RA, Douglas, KT. (2009). Discovery of novel inhibitors of Trypanosoma cruzitrans-sialidase from in silico screening. Bioorg Med Chem Lett, 19( 3), 589-96. eScholarID:1d18710 | DOI:10.1016/j.bmcl.2008.12.065

2008

  • Gbaj A., Walsh L., Rogert M.C., Sardarian A.R., Bichenkova E.V., Etchells L., Whitcombe D., Douglas K.T. (2008). Target-assembled exciplexes based on Scorpion oligonucleotides. Bioscience Reports, 28(1), 1-5. eScholarID:1d28138 | DOI:10.1042/BSR20070006
  • Mitchell F.L., Marks G.E., Bichenkova E.V., Douglas K.T., Bryce R.A. (2008). Molecular probes: insights into design and analysis from computational and physical chemistry. Biochem. Soc. Trans, 36 (1), 5598-5603. eScholarID:1d17010 | DOI:10.1016/j.tet.2008.03.045
  • Neres J, Bryce RA, Douglas KT. (2008). Rational drug design in parasitology: trans-sialidase as a case study for Chagas disease. Drug Discovery Today, 13[3/4], 110-117. eScholarID:1d16969
  • Suzuki M, Husimi Y, Komatsu H, Suzuki K, Douglas KT. (2008). Quantum Dot FRET Biosensors that Respond to pH, to Proteolytic or Nucleolytic Cleavage, to DNA Synthesis, or to a Multiplexing Combination. Journal of American Chemical Society, 130, 5720-5725. eScholarID:1d28180 | DOI:10.1021/ja710870e
  • Walsh L., Gbaj A., Etchells L., Douglas K.T., Bichenkova E.V. (2008). SNP Detection for Cytochrome P450 Alleles by Target-assembled Tandem Oligonucleotide Systems Based on Exciplexes. J. Biomol. Struct. Dyn, 25(6), 629-640. eScholarID:1d28166

2007

  • Gbaj A, Walsh L, Bichenkova EV, Etchells L, Douglas KT. (2007). A novel technology to detect CYP2CP*3 Alleles based on DNA-assembled exciplexes. eScholarID:2d2355
  • Neres J, Bonnet P, Bryce RA, Kotian P, Buschiazzo A, Alzari P, Douglas KT. (2007). Novel inhibitors of Trypanosoma cruzi trans-sialidase. eScholarID:2d2402
  • Valente C, Moreira R, Guedes R, Iley J, Jaffar M, Douglas KT. (2007). Design, synthesis and chemical reactivity of 1,4naphtoquinone derivatives as cysteine protease irreversible inhibitors. eScholarID:2d2405
  • Bichenkova E.V., Gbaj A., Walsh L., Savage H.E., Rogert C., Sardarian A.R., Etchells L., Douglas K.T. (2007). Detection of nucleic acids in situ: novel oligonucleotide analogue for target-assembled DNA-mounted exciplexes. Org. Biomol. Chem, 5(7), 1039-1051. eScholarID:1d27675
  • Kuznetsov N.A, Vladimir V.K, Zharkov D.O, Vorobjev Y.N, Nevinsky G.A, Douglas KT, Fedorova O.S. (2007). Pre-Steady-State Kinetic Study of Substrate Specificity of Escherichia coli Formamidopyrimidine-DNA glycosylase. Biochemistry, 46, 424-435. eScholarID:1d27528
  • McNally V, Rajabi M, Gbaj A, Stratford IJ, Edwards PN, Douglas KT, Bryce RA, Jaffar M, Freeman S. (2007). Design, synthesis and enzymatic evaluation of 6-bridged imidazolyluracil derivatives as inhibitors of human thymidine phosphorylase. J Pharm Pharmacol, 59( 4), 537-47. eScholarID:1d15563
  • Neres J, Bonnet P, Edwards PN, Kotian P.L, Buschiazzo A, Alzari P.M, Bryce RA, Douglas KT. (2007). Benzoic acid and pyridine derivatives as inhibitors of trypanosoma cruzi trans-sialidase. Bioorg Med Chem, 15, 2106-2119. eScholarID:1d15176
  • Valente C, Moreira R, Guedes R. C, Iley J, Jaffar M, Douglas KT. (2007). The 1,4-naphthoquinone scaffold in the design of cysteine protease inhibitors. Bioorg. Med. Chem, 15, 5340-5350. eScholarID:1d27799
  • Walsh L, Gbaj A, Savage HE, Bacigalupo M. C. R, Bichenkova EV, Douglas KT. (2007). Target-assembled ExciProbes: Application to DNA Detection at the Level of PCR Product and Plasmid DNA. Journal of Biomolecular Structure & Dynamics, 25,3, 219-229. eScholarID:1d27964

2006

  • Bichenkova E.V., Sardarian A.R., Wilton A.N., Bonnet P., Bryce R.A., Douglas K.T. (2006). Exciplex fluorescence emission from simple organic intramolecular constructs in non-polar and highly polar media as model systems for DNA-assembled exciplex detectors. Org. Biomol. Chem, 4(2), 367-378. eScholarID:1d12625
  • Gbaj A, Edwards PN, Reigan P, Freeman S, Jaffar M, Douglas KT. (2006). Thymidine phosphorylase from Escherichia coli: Tight-binding inhibitors as enzyme active-site titrants. Journal of Enzyme Inhibition and Medicinal Chemistry, 21(1), 69-73. eScholarID:1d27169
  • Kuznetsov N.A, Koval V.V, Nevinsky G.A, Douglas KT, Zharkov D.O, Fedorova O.S. (2006). Kinetic Conformational Analysis of Human 8-Oxoguanine-DNA Glycosylase. Journal of Biological Chemistry, 282, 1029-1038. eScholarID:1d27527
  • Neres J, Buschiazzo A, Alzari P.M, Walsh L, Douglas KT. (2006). Continuous fluorimetric assay for high-throughput screening of inhibitors of trans-sialidase from Trypanosoma cruzi. Analytical Biochemistry, 302-304. eScholarID:1d27526

2005

  • Bichenkova EV, Savage HE, Sardarian AR, Douglas KT. (2005). Target-assembled tandem oligonucleotide systems based on exciplexes for detecting DNA mismatches and single nucleotide polymorphisms. Biochem. Biophys. Res. Commun, 332, 956-964. eScholarID:1d11522 | DOI:10.1016/j.bbrc.2005.05.048
  • Bichenkova EV, Yu Xuan, Bhadra PK, Heissigerova H, Pope SJA, Coe BJ, Faulkner S, Douglas KT. (2005). DNA Mismatch Detection by Resonance Energy-Transfer between Ruthenium (II) and Osmium(ii) Tris (2,2'-bipyridyl) Chromophores. Inorg. Chem, 44, 4112-4114. eScholarID:1d11529
  • Hori Y, Rogert MC, Tanaka T, Kikuchi Y, Bichenkova EV, Wilton AN, Gbaj A, Douglas KT. (2005). Porphyrins and porphines bind strongly and specifically to tRNA, precursor tRNA and to M1 RNA and inhibit the ribonuclease P ribozyme reaction. Biochim. Biophys. Acta, 1730, 47-55. eScholarID:1d11536
  • Kuznetsov NA, Koval VV, Zharkov DO, Nevinsky GA, Douglas KT, Fedorova OS. (2005). Kinetics of substrate recognition and cleavage by human 8-oxoguanine-DNA glycosylase. Nucl. Acids Res, 33, 3919-31. eScholarID:1d11537 | DOI:10.1093/nar/gki694
  • Marks AHR, Bhadra PK, McDowell DG, French DJ, Bichenkova EV, Bryce RA, Douglas KT. (2005). Molecular Basis of Action of HyBeacon<sup>TM</sup> Fluorogenic Probes: a Spectroscopic and Molecular Dynamics Study. J. Biomol. Struct. Dynam, 23, 49-62. eScholarID:1d11483
  • Moreira R, Santana AB, Iley J, Neres J, Douglas KT, Horton PN, Hursthouse MB. (2005). Design, Synthesis, and Enzymatic Evaluation of N<sup>1</sup>-Acyloxyalkyl-and N<sup>1</sup>-Oxazolidin-2,4-dion-5-yl-Substituted β-lactams as Novel Inhibitors of Human Leukocyte Elastase. J. Med. Chem, 48, 4861-4870. eScholarID:1d11458 | DOI:10.1021/jm0501331
  • Parveen S, Khan M.O.F, Austin S.E, Croft S.L, Yardley V, Rock P, Douglas KT. (2005). Antitrypanosomal, Antileishmanial, and Antimalarial Activities of Quaternary Arylalkylammonium 2-Amino-4-Chlorophenyl Phenyl Sulfides, a New Class of Trypanothione Reductase Inhibitor, and of N-Acyl Derivatives of 2-Amino-4-Chlorophenyl Phenyl Sulfide. J. Med. Chem, 48, 8087-8097. eScholarID:1d26875 | DOI:10.1021/jm050819t
  • Reigan P, Edwards, PN, Gbaj A, Cole C, Barry ST, Page KM, Ashton SE, Luke RW, Douglas, KT, Stratford, IJ, Jaffar, M, Bryce, RA, Freeman, S. (2005). Aminoimidazolylmethyluracil analogues as potent inhibitors of thymidine phosphorylase and their bioreductive nitroimidazolyl prodrugs. Journal of Medicinal Chemistry, 48, 392-402. eScholarID:1d11542 | DOI:10.1021/jm049494r
  • Suzuki M, Ito Y, Sakata I, Sakai T, Husimi Y, Douglas KT. (2005). Caspase-3 sensitive signaling in vivo in apoptotic HeLa cells by chemically engineered intramolecular fluorescence resonance energy transfer (FRET) mutants of Green Fluorescent Protein. Biochem. Biophys. Res. Commun, 330, 454-460. eScholarID:1d11533
  • Zhang W, Suzuki M, Ito Y, Douglas KT. (2005). A Chemically Modified Green Fluorescent Protein that Responds to Cleavage of an Engineered Disulphide Bond by Fluorescence Resonance Energy Transfer (FRET)-Based Changes. Chem. Lett, 34, 766-7. eScholarID:1d11534

2001

  • Breusegem SY, Sadat-Ebrahimi S.E, Douglas KT, Bichenkova EV, Clegg R.M, Loontiens F.G. (2001). Experimental Precedent for the Need To Involve the Primary Hydration Layer of DNA in Lead Drug Design. Journal of Medicinal Chemistry, 44, 2503-2506. eScholarID:1d1075 | DOI:10.1021/jm0100943

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