View source for 7df5


==Human Galectin-3 CRD in complex with novel tetrahydropyran-based thiodisaccharide mimic inhibitor==
<StructureSection load='7df5' size='340' side='right'caption='[[7df5]], [[Resolution|resolution]] 1.08&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7df5]] is a 1 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=7DF5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7DF5 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]] 1.08&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=H5O:(2R,3R,4S,5R,6S)-2-(hydroxymethyl)-5-methoxy-6-[(3R,4R,5S)-4-oxidanyl-5-(4-pyrimidin-5-yl-1,2,3-triazol-1-yl)oxan-3-yl]sulfanyl-4-[4-[3,4,5-tris(fluoranyl)phenyl]-1,2,3-triazol-1-yl]oxan-3-ol'>H5O</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=7df5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7df5 OCA], [https://pdbe.org/7df5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7df5 RCSB], [https://www.ebi.ac.uk/pdbsum/7df5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7df5 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/LEG3_HUMAN LEG3_HUMAN] Galactose-specific lectin which binds IgE. May mediate with the alpha-3, beta-1 integrin the stimulation by CSPG4 of endothelial cells migration. Together with DMBT1, required for terminal differentiation of columnar epithelial cells during early embryogenesis (By similarity). In the nucleus: acts as a pre-mRNA splicing factor. Involved in acute inflammatory responses including neutrophil activation and adhesion, chemoattraction of monocytes macrophages, opsonization of apoptotic neutrophils, and activation of mast cells.<ref>PMID:15181153</ref> <ref>PMID:19594635</ref> <ref>PMID:19616076</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Galectin-3 is a member of a family of beta-galactoside-binding proteins. A substantial body of literature reports that galectin-3 plays important roles in cancer, inflammation, and fibrosis. Small-molecule galectin-3 inhibitors, which are generally lactose or galactose-based derivatives, have the potential to be valuable disease-modifying agents. In our efforts to identify novel galectin-3 disaccharide mimics to improve drug-like properties, we found that one of the monosaccharide subunits can be replaced with a suitably functionalized tetrahydropyran ring. Optimization of the structure-activity relationships around the tetrahydropyran-based scaffold led to the discovery of potent galectin-3 inhibitors. Compounds 36, 40, and 45 were selected for further in vivo evaluation. The synthesis, structure-activity relationships, and in vivo evaluation of novel tetrahydropyran-based galectin-3 inhibitors are described.

Synthesis, Structure-Activity Relationships, and In Vivo Evaluation of Novel Tetrahydropyran-Based Thiodisaccharide Mimics as Galectin-3 Inhibitors.,Xu L, Hartz RA, Beno BR, Ghosh K, Shukla JK, Kumar A, Patel D, Kalidindi N, Lemos N, Gautam SS, Kumar A, Ellsworth BA, Shah D, Sale H, Cheng D, Regueiro-Ren A J Med Chem. 2021 May 27;64(10):6634-6655. doi: 10.1021/acs.jmedchem.0c02001. Epub, 2021 May 14. PMID:33988358<ref>PMID:33988358</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7df5" style="background-color:#fffaf0;"></div>

==See Also==
*[[Galectin 3D structures|Galectin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Ghosh K]]
[[Category: Kumar A]]