4UIP

The complex structure of extracellular domain of EGFR with Repebody (rAC1).

4UIP の概要

• エントリーDOI: 10.2210/pdb4uip/pdb
• 分子名称: EPIDERMAL GROWTH FACTOR RECEPTOR, REPEBODY (RAC1), 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• 機能のキーワード: transferase
• 由来する生物種: HOMO SAPIENS (HUMAN); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 97757.03

構造登録者

Kang, Y.J.,Cha, Y.J.,Cho, H.S.,Lee, J.J.,Kim, H.S. (登録日: 2015-03-31, 公開日: 2015-11-25, 最終更新日: 2024-11-06)

主引用文献

Lee, J.,Choi, H.,Yun, M.,Kang, Y.,Jung, J.,Ryu, Y.,Kim, T.Y.,Cha, Y.,Cho, H.,Min, J.,Chung, C.,Kim, H.
Enzymatic Prenylation and Oxime Ligation for the Synthesis of Stable and Homogeneous Protein-Drug Conjugates for Targeted Therapy.
Angew.Chem.Int.Ed.Engl., 54:12020-, 2015

PubMed Abstract: Targeted therapy based on protein-drug conjugates has attracted significant attention owing to its high efficacy and low side effects. However, efficient and stable drug conjugation to a protein binder remains a challenge. Herein, a chemoenzymatic method to generate highly stable and homogenous drug conjugates with high efficiency is presented. The approach comprises the insertion of the CaaX sequence at the C-terminal end of the protein binder, prenylation using farnesyltransferase, and drug conjugation through an oxime ligation reaction. MMAF and an EGFR-specific repebody are used as the antitumor agent and protein binder, respectively. The method enables the precisely controlled synthesis of repebody-drug conjugates with high yield and homogeneity. The utility of this approach is illustrated by the notable stability of the repebody-drug conjugates in human plasma, negligible off-target effects, and a remarkable antitumor activity in vivo. The present method can be widely used for generating highly homogeneous and stable PDCs for targeted therapy.

PubMed: 26315561
DOI: 10.1002/ANIE.201505964

実験手法

X-RAY DIFFRACTION (2.95 Å)