DRUG TARGETING

[Fred R. Opperdoes]

>MESSAGE FROM root at cscdri.ren.nic.in
>
>"My Institute is mainly a Drug research Institute and therefore many
>compounds are synthesized, some putative antileishmanials as well. So for
>this purpose we are going to embark on screening them for
>antileishmanial activity in vitro. For this purpose I will be
>highly obliged to you for some information. Apart from
>certain enzyme targets which can be utilized for screening e.g.
>acid phosphatases, cysteine proteases, SOD, topoisomerases, to
>name a few well known ones I could find in literature, do you
>know of any other enzyme targets being used?
>               With regards to you,
>                                             Neeloo "
>Professor Jeffrey Shaw, General Manager ILN.
>Postal Address:               Personnel Mobile Phone......: 55-61-988-4573
>Caixa Postal 10529,           Fax/Phone Laboratory........: 55-91-226-6997
>71620-980 Brasilia, DF.       Phone Belem Laboratory (IEC): 55-91-211-4412
>Brazil.

The Steering Committee on Drugs for African Trypanosomiasis, Chagas'
Disease and Leishmaniasis of the Special Programme for Research and
Training in Tropical Diseases (TDR) of WHO has identified the following
enzymes as potential recombinant drug targets for use in combinatorial
chemistry and high throughput screening : SAMDC, Ornithine decarboxylase,
glycolytic enzymes, AGCPR, DGFR/TS. The Steering Committee on drugs for
Malaria has identified as useful targets the proteinases plasmepsin I, II
and falcipain, heme polimerizationin in the food vauole, inhibition of
enzymes of folate metabolism (DHFR, DHPS) and the enzymes of phospholipid
metabolism.

Paul Michels and collaborators in my laboratory have now overexpressed most
of the enzymes of the glycolytic pathway of several trypanosomatids: T.
brucei(TB) T.cruzi (TC) and L.mexicana (LM). These enzymes are: aldolase
(TB), triosephosphate isomerase (TB,LM), glyceraldehyde-phosphate
dehydrogenase (TB,TC,LM), phosphoglycerate kinase (TB), pyruvate kinase
(TB,LM), glycerol-3-phosphate dehydrogeanse (TB,LM). At present we are
working on the overexpression of hexokinase (TB) phosphofructokinase (TB)
and malate dehydrogenase of Phytomonas and the cloning and sequencing of
glycerol kinase (TB).

-------
Fred R. Opperdoes,
Research Unit for Tropical Diseases (TROP) and
Laboratory of Biochemistry (BCHM)
International Institute of Cellular and Molecular Pathology (ICP)
and Catholic University of Louvain (UCL)
Avenue Hippocrate 74-75, B-1200 Brussels, Belgium

Tel: ++32-2-764.74.39 (secretary) Fax: ++32-2-762.68.53
Tel: ++32-2-764.74.55 (direct)
E-mail:Opperdoes at trop.ucl.ac.be
Internet: http://www.icp.ucl.ac.be/ICP_en.html
          http://www.icp.ucl.ac.be/~opperd/Fred.html