8bdm
From Proteopedia
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[8bdm]] is a 12 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=8BDM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8BDM FirstGlance]. <br> | <table><tr><td colspan='2'>[[8bdm]] is a 12 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=8BDM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8BDM FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CAS:S-(DIMETHYLARSENIC)CYSTEINE'>CAS</scene>, <scene name='pdbligand=QE9:(2~{S},4~{R})-~{N}-[[2-(2-methoxyethoxy)-4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]-1-[(2~{R})-3-methyl-2-(3-methyl-1,2-oxazol-5-yl)butanoyl]-4-oxidanyl-pyrrolidine-2-carboxamide'>QE9</scene></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]] 2.021Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CAS:S-(DIMETHYLARSENIC)CYSTEINE'>CAS</scene>, <scene name='pdbligand=QE9:(2~{S},4~{R})-~{N}-[[2-(2-methoxyethoxy)-4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]-1-[(2~{R})-3-methyl-2-(3-methyl-1,2-oxazol-5-yl)butanoyl]-4-oxidanyl-pyrrolidine-2-carboxamide'>QE9</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=8bdm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8bdm OCA], [https://pdbe.org/8bdm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8bdm RCSB], [https://www.ebi.ac.uk/pdbsum/8bdm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8bdm 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=8bdm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8bdm OCA], [https://pdbe.org/8bdm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8bdm RCSB], [https://www.ebi.ac.uk/pdbsum/8bdm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8bdm ProSAT]</span></td></tr> | ||
</table> | </table> | ||
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Herein, we describe a systematic SAR- and SPR-investigation of the peptidomimetic hydroxy-proline based VHL-ligand VH032, from which most to-date published VHL-targeting PROTACs have been derived. This study provides for the first time a consistent data set which allows for direct comparison of structural variations including those which were so far hidden in patent literature. The gained knowledge about improved VHL binders was used to design a small library of highly potent BRD4-degraders comprising different VHL exit vectors. Newly designed degraders showed favorable molecular properties and significantly improved degradation potency compared to MZ1. | Herein, we describe a systematic SAR- and SPR-investigation of the peptidomimetic hydroxy-proline based VHL-ligand VH032, from which most to-date published VHL-targeting PROTACs have been derived. This study provides for the first time a consistent data set which allows for direct comparison of structural variations including those which were so far hidden in patent literature. The gained knowledge about improved VHL binders was used to design a small library of highly potent BRD4-degraders comprising different VHL exit vectors. Newly designed degraders showed favorable molecular properties and significantly improved degradation potency compared to MZ1. | ||
| - | Systematic Potency | + | Systematic Potency and Property Assessment of VHL Ligands and Implications on PROTAC Design.,Krieger J, Sorrell FJ, Wegener AA, Leuthner B, Machrouhi-Porcher F, Hecht M, Leibrock EM, Muller JE, Eisert J, Hartung IV, Schlesiger S ChemMedChem. 2023 Apr 17;18(8):e202200615. doi: 10.1002/cmdc.202200615. Epub 2023 , Feb 28. PMID:36749883<ref>PMID:36749883</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
VCB in complex with compound 26
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