View source for 8utk


==IL-23R minibinder - 23R-B04dslf02IB==
<StructureSection load='8utk' size='340' side='right'caption='[[8utk]], [[Resolution|resolution]] 1.94&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8utk]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8UTK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8UTK 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]] 1.94&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PG5:1-METHOXY-2-[2-(2-METHOXY-ETHOXY]-ETHANE'>PG5</scene>, <scene name='pdbligand=PG6:1-(2-METHOXY-ETHOXY)-2-{2-[2-(2-METHOXY-ETHOXY]-ETHOXY}-ETHANE'>PG6</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=8utk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8utk OCA], [https://pdbe.org/8utk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8utk RCSB], [https://www.ebi.ac.uk/pdbsum/8utk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8utk ProSAT]</span></td></tr>
</table>
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== Publication Abstract from PubMed ==
Interleukin (IL)-23 and IL-17 are well-validated therapeutic targets in autoinflammatory diseases. Antibodies targeting IL-23 and IL-17 have shown clinical efficacy but are limited by high costs, safety risks, lack of sustained efficacy, and poor patient convenience as they require parenteral administration. Here, we present designed miniproteins inhibiting IL-23R and IL-17 with antibody-like, low picomolar affinities at a fraction of the molecular size. The minibinders potently block cell signaling in vitro and are extremely stable, enabling oral administration and low-cost manufacturing. The orally administered IL-23R minibinder shows efficacy better than a clinical anti-IL-23 antibody in mouse colitis and has a favorable pharmacokinetics (PK) and biodistribution profile in rats. This work demonstrates that orally administered de novo-designed minibinders can reach a therapeutic target past the gut epithelial barrier. With high potency, gut stability, and straightforward manufacturability, de novo-designed minibinders are a promising modality for oral biologics.

Preclinical proof of principle for orally delivered Th17 antagonist miniproteins.,Berger S, Seeger F, Yu TY, Aydin M, Yang H, Rosenblum D, Guenin-Mace L, Glassman C, Arguinchona L, Sniezek C, Blackstone A, Carter L, Ravichandran R, Ahlrichs M, Murphy M, Pultz IS, Kang A, Bera AK, Stewart L, Garcia KC, Naik S, Spangler JB, Beigel F, Siebeck M, Gropp R, Baker D Cell. 2024 Jun 23:S0092-8674(24)00631-7. doi: 10.1016/j.cell.2024.05.052. PMID:38936360<ref>PMID:38936360</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8utk" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Baker D]]
[[Category: Bera AK]]
[[Category: Berger SA]]
[[Category: Kang A]]