 |
PDBsum entry 4zt3
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Ligase/ligase inhibitor
|
PDB id
|
|
|
|
4zt3
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
5-Fluoroimidazo[4,5-B]pyridine is a privileged fragment that conveys bioavailability to potent trypanosomal methionyl-Trna synthetase inhibitors.
|
|
|
Authors
|
|
Z.Zhang,
C.Y.Koh,
R.M.Ranade,
S.Shibata,
J.R.Gillespie,
M.A.Hulverson,
W.Huang,
J.Nguyen,
N.Pendem,
M.H.Gelb,
C.L.Verlinde,
W.G.Hol,
F.S.Buckner,
E.Fan.
|
|
|
Ref.
|
|
Acs Infect Dis, 2016,
2,
399-404.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
Fluorination is a well-known strategy for improving the bioavailability of drug
molecules. However, its impact on efficacy is not easily predicted. On the basis
of inhibitor-bound protein crystal structures, we found a beneficial
fluorination spot for inhibitors targeting methionyl-tRNA synthetase of
Trypanosoma brucei. In particular, incorporating 5-fluoroimidazo[4,5-b]pyridine
into inhibitors leads to central nervous system bioavailability and maintained
or even improved efficacy.
|
|
|
|
|
|
|
