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Prof. K.T.Douglas


Research

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

Teaching

Rational Drug Design
Protein structure and action
Enzyme mechanism and inhibition
Anticancer drug action

Administration

Director of Postgraduate Affairs
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

Society Membership

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, Department of Pharmacy (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, (summer) Orsay/C.N.R.S. (1978)
Honorary Professor, Nagasaki University (1983)
Matsumae International Fellow to Japan (1983)
Visiting Professor (Professeur Associate), 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 150 refereed publications the following are typical:

"Hoechst 33258 and its complex with the oligonucleotide d(CGCGAATTCGCG)2: 1H NMR
assignments and dynamics", by J.A. Parkinson, J. Barber, B.A. Buckingham, K.T. Douglas and
G.A. Morris, Mag. Res. Chem. (1992), 30, 1064-1069.

"C-terminally truncated human O6-alkylguanine-DNA-alkyltransferase retains enzyme activity",
by R.H. Elder, J. Tumelty, K.T. Douglas, G.P. Margison and J.A. Rafferty, Biochem. J., (1992)
285, 707-709.

"Rationally designed selective inhibitors of trypanothione reductase: phenothiazines and related
tricyclics as lead structures" by T.J. Benson, J.H. McKie, J. Garforth, A. Borges, A.H. Fairlamb
and K.T. Douglas, Biochem. J., 286, 9-11, (1992).

"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.

"Ferrocenopapain, an organometallic protein formed by site-specific inactivation of papain using
chloroacetylferrocene", by K.T. Douglas, O.S. Ejim and K. Taylor, J. Enz. Inhibition, (1992) 6,
233-242.

"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.

"Synthesis of substrate analogues for trypanothione reductase", by A.F. El-Waer, T. Benson and
K.T. Douglas, Int. J. Protein Res., (1993) 41, 141-146.

"A direct link between LY83583, a selective repressor of cyclic GMP formation, and glutathione
metabolism", by R.M. LÅînd, J.H. McKie and K.T. Douglas, Biochem. Pharmacol., (1993) 45,
2547-2549.

"A molecular model for cinnamyl alcohol dehydrogenase, a plant aromatic alcohol dehydrogenase
involved in lignification", by J.H. McKie, R. Jaouhari, K.T. Douglas, D. Goffner, C. Feuillet, J.
Grima-Pettenati, A.M. Boudet, M. Baltas and L. Gorrichon, Biochim. Biophys. Acta, (1993),
1202, 61-69.

"The glutamyl binding site of trypanothione reductase from Crithidia fasciculata: enzyme kinetic
properties of -glutamyl-modified substrate analogues, by A.F. El-Waer, K. Smith, J.H. McKie,
T. Benson, A.H. Fairlamb and K.T. Douglas, Biochim. Biophys. Acta, (1993), 1203, 93-98.

"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.

"Use of transferred nuclear Overhauser effect spectroscopy to measure the bound conformation
of an disulphide-replaced analogue of glutathione disulphide as an inhibitor of yeast glutathione
reductase", by K.J. Embrey, A. Mehta, S.J. Carrington, R. Jaouhari, J.H. McKie and K.T.
Douglas, Eur. J. Biochem. (1994) 221, 793-799.

"Rational Design of Peptide-Based Inhibitors of Trypanothione Reductase as Potential
Antitrypanosomal Drugs", by J. Garforth, J.H. McKie, R. Jaouhari, T.J. Benson, A.H. Fairlamb
and K.T. Douglas, Amino Acids, (1994) 6, 295-300.

"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. Bjîrnstedt, 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), accepted for publication.

"A Novel Convenient Route to the Naturally Occurring 3-Oxoacyl-L-homoserinelactones and
related Bacterial Autoinducers", by M. Dekhane, K. T. Douglas and P. Gilbert, Tetrahed.
Lett., (1996), 37, 1883-1884.

"Fluphenazine Photoaffinity Labelling of Binding Sites for Phenothiazine Inhibitors of
Trypanothione Reductase" by H. Yin, C. Chan, J. Garforth, K.T. Douglas, M.S. Bolgar, S.J.
Gaskell and A.H. Fairlamb, J. Chem. Soc. Chem. Commun., (1996), in press.

Further Information

Tel: +44 (0)161 275 2371
Fax: +44 (0)161 275 2396
E-mail: KTD@fs1.pa.man.ac.uk
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