6rw2
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Bicycle Toxin Conjugate bound to EphA2== | |
| + | <StructureSection load='6rw2' size='340' side='right'caption='[[6rw2]], [[Resolution|resolution]] 2.26Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6rw2]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RW2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6RW2 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]] 2.26Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=29N:1,1,1-(1,3,5-TRIAZINANE-1,3,5-TRIYL)TRIPROPAN-1-ONE'>29N</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=6rw2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rw2 OCA], [https://pdbe.org/6rw2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6rw2 RCSB], [https://www.ebi.ac.uk/pdbsum/6rw2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6rw2 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Bicycles are constrained bicyclic peptides that represent a promising binding modality for use in targeted drug conjugates. A phage display screen against EphA2, a receptor tyrosine kinase highly expressed in a number of solid tumors, identified a number of Bicycle families with low nanomolar affinity. A Bicycle toxin conjugate (BTC) was generated by derivatization of one of these Bicycles with the potent cytotoxin DM1 via a cleavable linker. This BTC demonstrated potent antitumor activity in vivo but was poorly tolerated, which was hypothesized to be the result of undesired liver uptake caused by poor physicochemical properties. Chemical optimization of a second Bicycle, guided by structural biology, provided a high affinity, metabolically stable Bicycle with improved physicochemical properties. A BTC incorporating this Bicycle also demonstrated potent antitumor activity and was very well tolerated when compared to the initial BTC. Phage display selection followed by chemical optimization of Bicycles can deliver potent drug conjugates with favorable pharmaceutical properties. | ||
| - | + | Identification and Optimization of EphA2-Selective Bicycles for the Delivery of Cytotoxic Payloads.,Mudd GE, Brown A, Chen L, van Rietschoten K, Watcham S, Teufel DP, Pavan S, Lani R, Huxley P, Bennett GS J Med Chem. 2020 Apr 2. doi: 10.1021/acs.jmedchem.9b02129. PMID:32202781<ref>PMID:32202781</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 6rw2" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Ephrin receptor 3D structures|Ephrin receptor 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Synthetic construct]] | ||
| + | [[Category: Brown DG]] | ||
| + | [[Category: Chen L]] | ||
| + | [[Category: Schroeder S]] | ||
Current revision
Bicycle Toxin Conjugate bound to EphA2
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