8tfp
From Proteopedia
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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. | 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 | + | 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 16;14(16):2849-2856. doi: , 10.1021/acschemneuro.3c00455. Epub 2023 Aug 3. PMID:37534714<ref>PMID:37534714</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
Fab from C10-S66K antibody in complex with carfentanil
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