8TFP

Fab from C10-S66K antibody in complex with carfentanil

Summary for 8TFP

• Entry DOI: 10.2210/pdb8tfp/pdb
• Descriptor: Light chain of Fab from C10-S66K antibody, Heavy chain of Fab from C10-S66K antibody, Carfentanil, ... (4 entities in total)
• Functional Keywords: antibody, fentanyl analogue, carfentanil, opioid., immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 94249.48

Authors

Pholcharee, T.,Wilson, I.A. (deposition date: 2023-07-11, release date: 2023-08-16, Last modification date: 2024-11-20)

Primary citation

Eubanks, L.M.,Pholcharee, T.,Oyen, D.,Natori, Y.,Zhou, B.,Wilson, I.A.,Janda, K.D.
An Engineered Human-Antibody Fragment with Fentanyl Pan-Specificity That Reverses Carfentanil-Induced Respiratory Depression.
Acs Chem Neurosci, 14:2849-2856, 2023

PubMed Abstract: 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.

PubMed: 37534714
DOI: 10.1021/acschemneuro.3c00455

Experimental method

X-RAY DIFFRACTION (1.78 Å)