Publication Date:
2015-04-21
Description:
Trypanosoma bruceiN-myristoyltransferase (TbNMT) is an attractive therapeutic target for the treatment of human African trypanosomiasis. Pyrazole sulfonamide (DDD85646), a potent inhibitor ofTbNMT, has been identified in previous studies; however, poor central nervous system exposure restricts its use to the haemolymphatic form (stage 1) of the disease. In order to identify new chemical matter, a fragment screen was carried out by ligand-observed NMR spectroscopy, identifying hits that occupy the DDD85646 binding site. Crystal structures of hits from this assay have been obtained in complex with the closely related NMT fromLeishmania major, providing a structural starting point for the evolution of novel chemical matter.
Electronic ISSN:
2053-230X
Topics:
Biology
,
Chemistry and Pharmacology
,
Geosciences
,
Physics
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