Probing the Complex
Binding Modes of the PPARγ
Partial Agonist 2‑Chloro‑<i>N</i>‑(3-chloro-4-((5-chlorobenzo[<i>d</i>]thiazol-2-yl)thio)phenyl)-4-(trifluoromethyl)benzenesulfonamide
(T2384) to Orthosteric and Allosteric Sites with NMR Spectroscopy
Travis
S. Hughes
Jinsai Shang
Richard Brust
Ian Mitchelle S. de Vera
Jakob Fuhrmann
Claudia Ruiz
Michael D. Cameron
Theodore M. Kamenecka
Douglas J. Kojetin
10.1021/acs.jmedchem.6b01340.s002
https://acs.figshare.com/articles/dataset/Probing_the_Complex_Binding_Modes_of_the_PPAR_Partial_Agonist_2_Chloro_i_N_i_3-chloro-4-_5-chlorobenzo_i_d_i_thiazol-2-yl_thio_phenyl_-4-_trifluoromethyl_benzenesulfonamide_T2384_to_Orthosteric_and_Allosteric_Sites_with_NMR_Spectroscopy/4207470
In
a previous study, a cocrystal structure of PPARγ bound
to 2-chloro-<i>N</i>-(3-chloro-4-((5-chlorobenzo[<i>d</i>]thiazol-2-yl)thio)phenyl)-4-(trifluoromethyl)benzenesulfonamide
(<b>1</b>, T2384) revealed two orthosteric pocket binding modes
attributed to a concentration-dependent biochemical activity profile.
However, <b>1</b> also bound an alternate/allosteric site that
could alternatively account for the profile. Here, we show ligand
aggregation afflicts the activity profile of <b>1</b> in biochemical
assays. However, ligand-observed fluorine (<sup>19</sup>F) and protein-observed
NMR confirms <b>1</b> binds PPARγ with two orthosteric
binding modes and to an allosteric site.
2016-10-26 00:00:00
activity profile
PPAR γ
site
show ligand aggregation
orthosteric binding modes
orthosteric pocket binding modes
-2-yl
thiazol
Complex Binding Modes
NMR
chloro