7QT0

Antibody FenAb136 - fentanyl complex

7QT0 の概要

• エントリーDOI: 10.2210/pdb7qt0/pdb
• 分子名称: Antibody heavy chain, Antibody light chain, 2-[2-[2-[2-[[5-oxidanylidene-5-[2-[4-[phenyl(propanoyl)amino]piperidin-1-yl]ethylamino]pentanoyl]amino]ethanoylamino]ethanoylamino]ethanoylamino]ethanoic acid, ... (4 entities in total)
• 機能のキーワード: antibody, immune system
• 由来する生物種: Mus musculus; 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 291731.89

構造登録者

Zeelen, J.P.,Straaten van, M.,Stebbins, C.E. (登録日: 2022-01-14, 公開日: 2023-05-24, 最終更新日: 2024-10-09)

主引用文献

Triller, G.,Vlachou, E.P.,Hashemi, H.,van Straaten, M.,Zeelen, J.P.,Kelemen, Y.,Baehr, C.,Marker, C.L.,Ruf, S.,Svirina, A.,Chandra, M.,Urban, K.,Gkeka, A.,Kruse, S.,Baumann, A.,Miller, A.K.,Bartel, M.,Pravetoni, M.,Stebbins, C.E.,Papavasiliou, F.N.,Verdi, J.P.
A trypanosome-derived immunotherapeutics platform elicits potent high-affinity antibodies, negating the effects of the synthetic opioid fentanyl.
Cell Rep, 42:112049-112049, 2023

PubMed Abstract: Poorly immunogenic small molecules pose challenges for the production of clinically efficacious vaccines and antibodies. To address this, we generate an immunization platform derived from the immunogenic surface coat of the African trypanosome. Through sortase-based conjugation of the target molecules to the variant surface glycoprotein (VSG) of the trypanosome surface coat, we develop VSG-immunogen array by sortase tagging (VAST). VAST elicits antigen-specific memory B cells and antibodies in a murine model after deploying the poorly immunogenic molecule fentanyl as a proof of concept. We also develop a single-cell RNA sequencing (RNA-seq)-based computational method that synergizes with VAST to specifically identify memory B cell-encoded antibodies. All computationally selected antibodies bind to fentanyl with picomolar affinity. Moreover, these antibodies protect mice from fentanyl effects after passive immunization, demonstrating the ability of these two coupled technologies to elicit therapeutic antibodies to challenging immunogens.

PubMed: 36719797
DOI: 10.1016/j.celrep.2023.112049

実験手法

X-RAY DIFFRACTION (2.07 Å)