6u85: Difference between revisions
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==Site-specific lysine arylation as an alternative bioconjugation strategy for chemically programmed antibodies and antibody-drug conjugates== | |||
<StructureSection load='6u85' size='340' side='right'caption='[[6u85]], [[Resolution|resolution]] 2.78Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6u85]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6U85 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6U85 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6u85 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6u85 OCA], [http://pdbe.org/6u85 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6u85 RCSB], [http://www.ebi.ac.uk/pdbsum/6u85 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6u85 ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
By exploiting a uniquely reactive lysine residue (Lys99) for site-specific attachment of small molecules, the humanized catalytic antibody h38C2 has been used as bioconjugation module in the assembly of chemically programmed antibodies and antibody-drug conjugates. Treatment of h38C2 with beta-lactam-functionalized small molecules has been previously shown to result in covalent conjugation by selective formation of a stable amide bond with the epsilon-amino group of the Lys99 residue. Here we report that heteroaryl methylsulfonyl (MS-PODA)-functionalized small molecules represent an alternative bioconjugation strategy through highly efficient, site-specific, and stable arylation of the Lys99 residue. A set of chemically programmed antibodies and antibody-drug conjugates assembled by Lys99 arylation provided proof-of-concept for the therapeutic utility of this alternative bioconjugation strategy. While being equally effective as beta-lactam-functionalized ligands for bioconjugation with catalytic antibody h38C2, the MS-PODA moiety offers distinct synthetic advantages, making it highly attractive. | |||
Site-Specific Lysine Arylation as an Alternative Bioconjugation Strategy for Chemically Programmed Antibodies and Antibody-Drug Conjugates.,Hwang D, Tsuji K, Park H, Burke TR Jr, Rader C Bioconjug Chem. 2019 Nov 1. doi: 10.1021/acs.bioconjchem.9b00609. PMID:31675216<ref>PMID:31675216</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6u85" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Park, H]] | |||
[[Category: Rader, C]] | [[Category: Rader, C]] | ||
[[Category: | [[Category: Antibody]] | ||
[[Category: Immune system]] | |||
[[Category: Kringle domain]] | |||
[[Category: Phage display]] | |||
[[Category: Receptor tyrosine kinase-like orphan receptor]] | |||
[[Category: Ror2]] | |||
[[Category: Scfv]] | |||
[[Category: Single chain fv]] | |||
