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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4zt7|4zt7]], [[4zt6|4zt6]], [[4zt4|4zt4]], [[4zt3|4zt3]], [[4zt2|4zt2]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4zt7|4zt7]], [[4zt6|4zt6]], [[4zt4|4zt4]], [[4zt3|4zt3]], [[4zt2|4zt2]]</td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Methionine--tRNA_ligase Methionine--tRNA ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.1.1.10 6.1.1.10] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Methionine--tRNA_ligase Methionine--tRNA ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.1.1.10 6.1.1.10] </span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4zt5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zt5 OCA], [http://pdbe.org/4zt5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4zt5 RCSB], [http://www.ebi.ac.uk/pdbsum/4zt5 PDBsum]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4zt5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zt5 OCA], [http://pdbe.org/4zt5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4zt5 RCSB], [http://www.ebi.ac.uk/pdbsum/4zt5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4zt5 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
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== Publication Abstract from PubMed == | |||
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. | |||
5-Fluoroimidazo[4,5-b]pyridine Is a Privileged Fragment That Conveys Bioavailability to Potent Trypanosomal Methionyl-tRNA Synthetase Inhibitors.,Zhang Z, Koh CY, Ranade RM, Shibata S, Gillespie JR, Hulverson MA, Huang W, Nguyen J, Pendem N, Gelb MH, Verlinde CL, Hol WG, Buckner FS, Fan E ACS Infect Dis. 2016 Jun 10;2(6):399-404. doi: 10.1021/acsinfecdis.6b00036. Epub , 2016 Apr 11. PMID:27627628<ref>PMID:27627628</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4zt5" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Revision as of 12:42, 19 October 2016
Trypanosoma brucei methionyl-tRNA synthetase in complex with inhibitor (2S)-N-(3,5-dichlorobenzyl)-N'-(1H-imidazo[4,5-b]pyridin-2-yl)-2-methylpropane-1,3-diamine (Chem 1655)Trypanosoma brucei methionyl-tRNA synthetase in complex with inhibitor (2S)-N-(3,5-dichlorobenzyl)-N'-(1H-imidazo[4,5-b]pyridin-2-yl)-2-methylpropane-1,3-diamine (Chem 1655)
Structural highlights
Publication Abstract from PubMedFluorination 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. 5-Fluoroimidazo[4,5-b]pyridine Is a Privileged Fragment That Conveys Bioavailability to Potent Trypanosomal Methionyl-tRNA Synthetase Inhibitors.,Zhang Z, Koh CY, Ranade RM, Shibata S, Gillespie JR, Hulverson MA, Huang W, Nguyen J, Pendem N, Gelb MH, Verlinde CL, Hol WG, Buckner FS, Fan E ACS Infect Dis. 2016 Jun 10;2(6):399-404. doi: 10.1021/acsinfecdis.6b00036. Epub , 2016 Apr 11. PMID:27627628[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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