6XXP

Crystal structure of NB37, a nanobody targeting prostate specific membrane antigen

6XXP の概要

• エントリーDOI: 10.2210/pdb6xxp/pdb
• 分子名称: NB_37 (2 entities in total)
• 機能のキーワード: nanobody, prostate-specific membrane antigen, antibody drug conjugate, cancer imaging, anti-cancer drugs., antitumor protein
• 由来する生物種: Camelus dromedarius (Arabian camel)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 15715.04

構造登録者

Shahar, A.,Rosenfeld, L.,Papo, N. (登録日: 2020-01-28, 公開日: 2020-06-10, 最終更新日: 2024-11-06)

主引用文献

Rosenfeld, L.,Sananes, A.,Zur, Y.,Cohen, S.,Dhara, K.,Gelkop, S.,Ben Zeev, E.,Shahar, A.,Lobel, L.,Akabayov, B.,Arbely, E.,Papo, N.
Nanobodies Targeting Prostate-Specific Membrane Antigen for the Imaging and Therapy of Prostate Cancer.
J.Med.Chem., 63:7601-7615, 2020

PubMed Abstract: The repertoire of methods for the detection and chemotherapeutic treatment of prostate cancer (PCa) is currently limited. Prostate-specific membrane antigen (PSMA) is overexpressed in PCa tumors and can be exploited for both imaging and drug delivery. We developed and characterized four nanobodies that present tight and specific binding and internalization into PSMA cells and that accumulate specifically in PSMA tumors. We then conjugated one of these nanobodies to the cytotoxic drug doxorubicin, and we show that the conjugate internalizes specifically into PSMA cells, where the drug is released and induces cytotoxic activity. studies show that the extent of tumor growth inhibition is similar when mice are treated with commercial doxorubicin and with a 42-fold lower amount of the nanobody-conjugated doxorubicin, attesting to the efficacy of the conjugated drug. These data highlight nanobodies as promising agents for the imaging of PCa tumors and for the targeted delivery of chemotherapeutic drugs.

PubMed: 32442375
DOI: 10.1021/acs.jmedchem.0c00418

実験手法

X-RAY DIFFRACTION (1.5 Å)