H. Ko et al. / Bioorg. Med. Chem. 17 (2009) 5298–5311
5311
7. Amisten, S.; Melander, O.; Wihlborg, A. K.; Berglund, G.; Erlinge, D. Eur. Heart J.
2007, 28, 13.
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formed by the following amino acid residues: Arg274, Lys277,
Arg253, Glu278, Tyr249, Leu281, Gln22, Ile25, Pro26, Phe74,
Lys77, Ile78, Leu79, Asp81, Ser82, Leu84, Ser97, Ala98, Leu100,
Phe101, Cys172, Ile173, and Glu174. The InducedFit docking ap-
proach was utilized to initial docking of 1 to the P2Y14 receptor.
The receptor grid generation was performed for the box with auto-
matically determined side and with a center in the centroid of the
binding site identified with the SITEMAP. The default values were ap-
plied for all other parameters.
The model of the P2Y14 receptor with 1 docked was subjected to
Monte-Carlo Multiple Minimum (MCMM) calculations. The confor-
mations of the side chains of residues located within 5 Å from 1 were
refined by Mixed torsional/Low-mode sampling method, a shell of
residues located within 2 Å was used. The following parameters
were applied: MMFFs force field, water as an implicit solvent, a max-
imum of 500 iterations of the Polak-Ribier conjugate gradient mini-
mization method was used with a convergence threshold of
0.05 kJ molꢀ1 Åꢀ1, the number of conformational search steps = 200,
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the energy window for saving structures = 100 kJ molꢀ1
.
The GLIDE program of Schrödinger suite and the P2Y14—1 com-
plex obtained were utilized to dock 17a to the P2Y14 receptor.
The extra precision (XP) mode was used. The grid generation was
performed for the box with automatically determined side. The
center of the box was defined as the centroid of UDPG, 1. The li-
gand flexibility was allowed.
22. Besada, P.; Shin, D. H.; Costanzi, S.; Ko, H.; Mathé, C.; Gagneron, J.; Gosselin, G.;
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Acknowledgments
Mass spectral measurements were carried out by Dr. John Lloyd
and Dr. Noel Whittaker and NMR by Wesley White (NIDDK). We
thank Dr. Stefano Costanzi (NIDDK) for helpful discussion and Dr.
Sonia de Castro, Dr. T. Santhosh Kumar, Nathaniel Kim, and Deep-
mala Kumar (all of NIDDK) and Lauren Burianek (UNC) for techni-
cal assistance. This research was supported in part by the
Intramural Research Program of the NIH, National Institute of Dia-
betes and Digestive and Kidney Diseases. This work was supported
by National Institutes of Health Grant GM38213 to T.K. Harden.
26. Joshi, B. V.; Melman, A.; Mackman, R. L.; Jacobson, K. A. Nucleosides, Nucleotides,
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Supplementary data
Details of synthesis and characterization of analogues of 1,
including monofluorinated glucose derivatives and other sugar
derivatives are available. Supplementary data associated with this
article can be found, in the online version, at doi:10.1016/
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