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Identification and structure solution of fragment hits against kinetoplastid N ‐myristoyltransferase
Author(s) -
Robinson David A.,
Wyatt Paul G.
Publication year - 2015
Publication title -
acta crystallographica section f
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.572
H-Index - 37
ISSN - 2053-230X
DOI - 10.1107/s2053230x15003040
Subject(s) - trypanosoma brucei , stereochemistry , sulfonamide , chemistry , computational biology , leishmania , ligand (biochemistry) , biochemistry , biology , receptor , parasite hosting , world wide web , gene , computer science
Trypanosoma bruceiN ‐myristoyltransferase ( Tb NMT) is an attractive therapeutic target for the treatment of human African trypanosomiasis. Pyrazole sulfonamide (DDD85646), a potent inhibitor of Tb NMT, 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 from Leishmania major , providing a structural starting point for the evolution of novel chemical matter.