8tfp: Difference between revisions
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The | ==Fab from C10-S66K antibody in complex with carfentanil== | ||
<StructureSection load='8tfp' size='340' side='right'caption='[[8tfp]], [[Resolution|resolution]] 1.78Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8tfp]] is a 4 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=8TFP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8TFP 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]] 1.78Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=84K:methyl+1-(2-phenylethyl)-4-(N-phenylpropanamido)piperidine-4-carboxylate'>84K</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=8tfp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8tfp OCA], [https://pdbe.org/8tfp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8tfp RCSB], [https://www.ebi.ac.uk/pdbsum/8tfp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8tfp ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The opioid overdose crisis primarily driven by potent synthetic opioids resulted in more than 500,000 deaths in the US over the last 20 years. Though naloxone, a short-acting medication, remains the primary treatment option for temporarily reversing opioid overdose effects, alternative countermeasures are needed. Monoclonal antibodies present a versatile therapeutic opportunity that can be tailored to synthetic opioids and help prevent post-treatment renarcotization. The ultrapotent analog carfentanil is especially concerning due to its unique pharmacological properties. With this in mind, we generated a fully human antibody through a drug-specific B cell sorting strategy with a combination of carfentanil and fentanyl probes. The resulting pan-specific antibody was further optimized through scFv phage display, producing C10-S66K. This monoclonal antibody displays high affinity to carfentanil, fentanyl, and other analogs and reversed carfentanil-induced respiratory depression. Additionally, X-ray crystal structures with carfentanil and fentanyl bound provided structural insight into key drug:antibody interactions. | |||
An Engineered Human-Antibody Fragment with Fentanyl Pan-Specificity That Reverses Carfentanil-Induced Respiratory Depression.,Eubanks LM, Pholcharee T, Oyen D, Natori Y, Zhou B, Wilson IA, Janda KD ACS Chem Neurosci. 2023 Aug 3. doi: 10.1021/acschemneuro.3c00455. PMID:37534714<ref>PMID:37534714</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 8tfp" style="background-color:#fffaf0;"></div> | ||
[[Category: Pholcharee | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Pholcharee T]] | |||
[[Category: Wilson IA]] | |||
Revision as of 11:31, 16 August 2023
Fab from C10-S66K antibody in complex with carfentanilFab from C10-S66K antibody in complex with carfentanil
Structural highlights
Publication Abstract from PubMedThe opioid overdose crisis primarily driven by potent synthetic opioids resulted in more than 500,000 deaths in the US over the last 20 years. Though naloxone, a short-acting medication, remains the primary treatment option for temporarily reversing opioid overdose effects, alternative countermeasures are needed. Monoclonal antibodies present a versatile therapeutic opportunity that can be tailored to synthetic opioids and help prevent post-treatment renarcotization. The ultrapotent analog carfentanil is especially concerning due to its unique pharmacological properties. With this in mind, we generated a fully human antibody through a drug-specific B cell sorting strategy with a combination of carfentanil and fentanyl probes. The resulting pan-specific antibody was further optimized through scFv phage display, producing C10-S66K. This monoclonal antibody displays high affinity to carfentanil, fentanyl, and other analogs and reversed carfentanil-induced respiratory depression. Additionally, X-ray crystal structures with carfentanil and fentanyl bound provided structural insight into key drug:antibody interactions. An Engineered Human-Antibody Fragment with Fentanyl Pan-Specificity That Reverses Carfentanil-Induced Respiratory Depression.,Eubanks LM, Pholcharee T, Oyen D, Natori Y, Zhou B, Wilson IA, Janda KD ACS Chem Neurosci. 2023 Aug 3. doi: 10.1021/acschemneuro.3c00455. PMID:37534714[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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