Research articleIn silico drug re-purposing against African sleeping sickness using GlcNAc-PI de-N-acetylase as an experimental target
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Background
The protozoa are among the most diverse and ancient group of organisms in the eukaryotic kingdom (Sogin et al., 1989). Many of their members are parasitic, of which some belonging to the family Trypanosomatidae (Trypanosoma brucei, Trypanosoma cruzi, Leishmania Species) cause some of the worst diseases in humans and their domestic livestock. There are two sub species of the genus Trypanosoma, T.brucei gambiense which causes African sleeping sickness in humans and T. brucei brucei which causes
Material and methods
The flowchart of steps of our study of re-purposing of drugs is given in Fig. 1. The drug target, GlcNAc-PI de-N-acetylase, sequence (TTDR00597) for T.brucei has been taken from the Therapeutic Target Database (TTD) (Chen et al., 2002). The Uniprot Id of the target sequence is Q8I8A5. Then BLASTP (Altschul et al., 1990) against RefSeq protein sequence database has been performed to detect homologues of this target protein sequence of T. brucei. A Web-based tool, SMART is used to find the active
Results and discussion
The results, after applying the sequential steps of drug re-purposing, are as follow:
Acknowledgements
MR is thankful to the Council of Scientific & Industrial Research (CSIR), India for the financial support through CSIR Senior Research Fellowship. The authors would also like to acknowledge and thank the two anonymous reviewers, whose valuable and incisive suggestions led to a vast improvement of this paper.
References (43)
- et al.
Synthesis of potential metal-binding group compounds to examine the zinc dependency of the de-N-acety-lase metalloenzyme in Trypanosoma brucei
Carbohydr. Res.
(2011) The process of structure-based drug design
Chem. Biol.
(2003)- et al.
Basic local alignment search tool
J. Mol. Biol.
(1990) - et al.
Cloning of Trypanosoma brucei and Leishmania major genes encoding the GlcNAc-Phosphatidylinositopl De-N-acetylase of glycosylphosphatidylinositol biosynthesis that is essential to the African Sleeping Sickness parasite
J. Biol. Chem.
(2002) - et al.
Molecular analysis of archived blood slides reveals an atypical human Trypanosoma infection
Diagn. Microbiol. Infect. Dis.
(2008) - et al.
Structural analysis of the glycosyl-phosphatidylinositol membrane anchor of the merozoite surface proteins-1 and -2 of Plasmodium falciparum
Mol. Biochem. Parasitol.
(1996) - et al.
A geometric approach to macromolecule-ligand interactions
J. Mol. Biol.
(1982) - et al.
The major surface antigens of Entamoeba histolytica trophozoites are GPI-anchored proteophosphoglycans
J. Mol. Biol.
(2000) - et al.
Identification of the lipid moiety and further characterization of the novel lipophosphoglycan-like glycoconjugates of Trichomonas vaginalis and Trichomonas foetus
Arch. Biochem. Biophys.
(1994) - et al.
Molecular structure of the low molecular weight antigen of Toxoplasma gondii: a glucose a 1-4N-acetylgalactosamine makes free glycosyl-phosphatidylinositols highly immunogenic
J. Mol. Biol.
(1997)