8sz3
From Proteopedia
(Difference between revisions)
| Line 5: | Line 5: | ||
<table><tr><td colspan='2'>[[8sz3]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8SZ3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8SZ3 FirstGlance]. <br> | <table><tr><td colspan='2'>[[8sz3]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8SZ3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8SZ3 FirstGlance]. <br> | ||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.32Å</td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.32Å</td></tr> | ||
| - | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=X18:N-[( | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=X18:~{N}-[(1~{S})-1-(5-bromanylpyridin-2-yl)ethyl]-3-[(2~{R})-3,3-dimethylbutan-2-yl]-2-oxidanylidene-1~{H}-benzimidazole-5-carboxamide'>X18</scene></td></tr> |
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8sz3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8sz3 OCA], [https://pdbe.org/8sz3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8sz3 RCSB], [https://www.ebi.ac.uk/pdbsum/8sz3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8sz3 ProSAT]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8sz3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8sz3 OCA], [https://pdbe.org/8sz3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8sz3 RCSB], [https://www.ebi.ac.uk/pdbsum/8sz3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8sz3 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| Line 14: | Line 14: | ||
B3GNT2 is responsible for elongation of cell surface long-chain polylactosamine, which influences the regulation of the immune response, making it an attractive target for immunomodulation. In the development of amide containing B3GNT2 inhibitors guided by structure-based drug design, imidazolones were found to successfully serve as amide bioisosteres. This novel imidazolone isosteric strategy alleviated torsional strain of the amide bond on binding to B3GNT2 and improved potency, isoform selectivity, as well as certain physicochemical and pharmacokinetic properties. Herein, we present the synthesis, SAR, X-ray cocrystal structures, and in vivo PK properties of imidazol-4-ones in the context of B3GNT2 inhibition. | B3GNT2 is responsible for elongation of cell surface long-chain polylactosamine, which influences the regulation of the immune response, making it an attractive target for immunomodulation. In the development of amide containing B3GNT2 inhibitors guided by structure-based drug design, imidazolones were found to successfully serve as amide bioisosteres. This novel imidazolone isosteric strategy alleviated torsional strain of the amide bond on binding to B3GNT2 and improved potency, isoform selectivity, as well as certain physicochemical and pharmacokinetic properties. Herein, we present the synthesis, SAR, X-ray cocrystal structures, and in vivo PK properties of imidazol-4-ones in the context of B3GNT2 inhibition. | ||
| - | Imidazolone as an Amide Bioisostere in the Development of beta-1,3-N-Acetylglucosaminyltransferase 2 (B3GNT2) Inhibitors.,Jackson JJ, Siegmund AC, Bai WJ, Reed AB, Birkholz AB, Campuzano IDG, Crequer-Grandhomme A, Hu R, Modak RV, Sudom A, Javier N, Sanders C, Lo MC, Xie F, Cee VJ, Manzanillo P, Allen JG J Med Chem. 2023 | + | Imidazolone as an Amide Bioisostere in the Development of beta-1,3-N-Acetylglucosaminyltransferase 2 (B3GNT2) Inhibitors.,Jackson JJ, Siegmund AC, Bai WJ, Reed AB, Birkholz AB, Campuzano IDG, Crequer-Grandhomme A, Hu R, Modak RV, Sudom A, Javier N, Sanders C, Lo MC, Xie F, Cee VJ, Manzanillo P, Allen JG J Med Chem. 2023 Dec 14;66(23):16120-16140. doi: 10.1021/acs.jmedchem.3c01517. , Epub 2023 Nov 21. PMID:37988652<ref>PMID:37988652</ref> |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
Current revision
Structure of human beta 1,3-N-acetylglucosaminyltransferase 2 with compound 7j
| |||||||||||
