K T Douglas MA(Oxford) PhD(Kent at Canterbury) Tel: +44 (0)161 275 2371 FAX: +44 (0)161 275 2396 E-mail: KTD@fs1.pa.man.ac.uk

Research

Rational drug design/molecular graphics
Mechanistic enzymology and enzyme kinetics
Design of enzyme inhibitors as potential drug leads
Design of DNA and RNA ligands and their high-field NMR analysis
New chemical cleavage methods for nucleic acids
Synthesis of potential drug molecules
Disease interests: cancer, trypanosomiasis, leishmaniasis, malaria
DNA repair

Teaching

Rational drug design
Protein structure and action
Enzyme mechanism and inhibition
Anticancer drug action

Administration

Director of Postgraduate Studies
Chairman, Teaching Standards Committee
Head, Drug Action and Design Group

Qualifications

B.A. (Hons.) Chemistry, Balliol College, Oxford University, 1966-1970
M.A., University of Oxford, 1973
Ph.D. Biological Chemistry, University of Kent at Canterbury, 1970-73
F.R.S.C, C.Chem; 1997

Society Membership

Fellow of the Royal Society of Chemistry
The Biochemical Society (London)
Society for Drug Research
British Association for Cancer Research
United Kingdom Association of Pharmaceutical Scientists

Brief Career Details

Professor of Medicinal Chemistry, School of Pharmacy and Pharmaceutical Sciences (1987-present)
Head of Department of Pharmacy (1991-1994)
Lecturer in Biological Chemistry, University of Essex, UK (1978-1987)
Associate Professor of Chemistry and Biochemistry, Duquesne University, Pittsburgh, USA
(1978)
Assistant Professor of Chemistry and Biochemistry, Duquesne University, Pittsburgh, USA
(1975-1978)
Research Associate, Department of Chemistry, University of Chicago (1973-1975)

External Honours and Appointments

Professeur d'Echange, University de Paris-Sud, Orsay/C.N.R.S. (1978)
Honorary Professor, Nagasaki University (1983)
Matsumae Medal and International Fellow to Japan (1983)
Professeur Associé, University Paul-Sabatier, Toulouse (1991-92)

Awards

Awarded Sir Hans Sloane Medal for highest mark in 1966 A-level, GCE in Chemistry, Physics
and Biology (N.Ireland). Also awarded Royal Institute of Chemistry prize for highest individual
mark (boys) in GCE A-level, Chemistry, 1966.

Recent Publications

Of approximately 160 refereed publications the following are typical:

"Improved efficiency and selectivity in peptide synthesis: use of triethylsilane as a carbocation
scavenger in deprotection of t-butyl esters and t-butoxycarbonyl-protected sites", by A. Mehta,
R. Jaouhari, T.J. Benson and K.T. Douglas, Tetrahed. Lett., (1992) 33, 5441-5444.

"Sequence-dependent reactivity of linear DNA to chemical cleavage by Cu(II):thiol combinations
including cysteine or glutathione", by D.C.A. John and K.T. Douglas, Biochem. J., (1993) 289,
463-468.

"Site-directed mutagenesis of glutamic acid 172 to glutamine completely inactivated human
O⁶-alkylguanine-DNA-alkyltransferase", by J.A. Rafferty, J. Tumelty, R.H. Elder, M. Skorvaga,
G.P. Margison and K.T. Douglas, Biochem. Biophys. Res. Commun. (1994) 199, 285-291.

"Photoaffinity labelling of the active-site of the rat liver glutathione S-transferases 3-3 and 1-1 and
human glutathione transferase A1-1", by R.J. Cooke, K.T. Douglas, J.H. McKie, M.D. King, B.
Coles, B. Ketterer, R. Bjørnstedt, B. Mannervik, Biochem. J. (1994) 302, 383-390.

"Molecular Design of DNA-directed Ligands with Specific Interactions: Solution NMR Studies
of the Interaction of a meta-hydroxy analogue of Hoechst 33258 with d(CGCGAATTCGCG)₂,
by J.A. Parkinson, S.E. Ebrahimi, J.H. McKie and K.T. Douglas, Biochemistry (1994) 33,
8442-8452.

"Rational Drug Design in Parasitology", by K.T. Douglas, Parasitology Today (1994) 10,
389-392.

"A Homology Model of the three-dimensional structure of Human O⁶-alkylguanine
DNA-alkyltransferase based on the crystal structure of the C-terminal domain of the
Ada protein from Escherichia coli",
by J.E.A. Wibley, J.H. McKie, K.Embrey, D.S. Marks, K.T. Douglas, M.H. Moore,
P.C.E. Moody, Anti-Cancer Drug Design, 1995, 10, 75-95.

"Synthesis, DNA-binding, footprinting and in vitro antitumour activity of a meta-hydroxy
analogue of Hoechst 33258", by S. E. Sadat Ebrahimi, M. C. Bibby, K. R. Fox, and K. T.
Douglas, Anti-Cancer Drug Design, 1995, 10, 463-479.

"Site-Directed Mutagenesis of a Serine Residue in Cinnamyl Alcohol Dehydrogenase, a Plant
NADPH-Dependent Dehydrogenase, Affects the Specificity for the Coenzyme", by V.
Lauvergeat, K. Kennedy, C. Feuillet, J. H. McKie, L.Gorrichon, M. Baltas, A. M. Boudet, J.
Grima-Pettenati and K. T. Douglas, Biochemistry,1995, 34, 12426-434.

"Predictability of Designing Specific Binding Interactions for DNA Minor Groove Ligands from
NMR Spectroscopy and Molecular Modelling: A Copper (II)-Activated DNA
Cleaver based on Hoechst 33258", J. A. Parkinson, S. Sadat-Ibrahimi, A. Wilton, J. H.
McKie, J. Andrews and K. T. Douglas, Biochemistry, (1995) 34, 16240-44.

"A Homology Model of the Id-3 helix-loop-helix domain as a basis for structure-function
predictions", by J. E. A. Wibley, R. Deed, M. Jasiok, K. T. Douglas, and J. D. Norton, Biochim.
Biophys. Acta, (1996)1294, 138-146

"A Unique Binding Site for Bis-benzimidazoles on transfer RNA" by S.E.Ebrahimi, A.N.Wilton, K.T.Douglas, Chem.Commun.,(1997),385-386

"A Common Chemical Mechanism Used for DNA cleavage by Copper (II)Activated by Thiols and Ascorbate is Distinct from that for Cu(II) :Hydrogen Peroxide Cleavage", by D.C.A. John and K.T.Douglas, Transition Metal Chem.,(1996)21,460-463

"Structural Investigation of a Binary-Addressed Oligonucleotide System Juxtaposing Pyrene and Perfluouoazide Units by means of High-Field NMR spectroscopy and Molecular Modeling" by E.V.Bichenkova, D.S.Marks, S.G.Lokhov, M.I. Dobrikov, V.Vlassov and K.T.Douglas, J Biomol. Struct.Dynamics(1997), 15, 307-320

"Phenothiazine Inhibitors of Trypanothione Reductase as Potential Antritrypanosomal and Antileishmanial Drugs" by C.C. Chan, H.Yin, J.Garforth, J.H.McKie, R.Jaohari, P.Speers, K.T.Douglas, P.J.Rock, V.Yardley, S.L.Croft and A.H.Fairlamb, J.Med.Chem.,(1998)41, 148-156

"A Rational Drug Design Approach to Overcoming Drug Resistance: Application to Pyrimethamine in Malaria" by J.H.McKie, K.T.Douglas, C.Chan, S.A.Roser, R.Yates, M.Reid, J.E Hyde, M.JDascombe, Y.Yuthavong and W.Sirawaraporn, J.Med.Chem.,(1998) 41, 1367-1370