7RH3

Co-crystallization of human galectin-3 CRD complex with Methyl 2-O-(2-nitro-4-chloro)-benzoyl-3-O-toluoyl-b-D-talopyranoside

7RH3 の概要

• エントリーDOI: 10.2210/pdb7rh3/pdb
• 分子名称: Galectin-3, CHLORIDE ION, methyl 2-O-(4-chloro-2-nitrobenzoyl)-3-O-(4-methylbenzoyl)-beta-D-talopyranoside, ... (4 entities in total)
• 機能のキーワード: carbohydrates-binding protein, sugar binding protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 16266.45

構造登録者

Collins, P.M.,Kishor, C.,Blanchard, H. (登録日: 2021-07-16, 公開日: 2022-07-13, 最終更新日: 2023-10-18)

主引用文献

Bum-Erdene, K.,Collins, P.M.,Hugo, M.W.,Tarighat, S.S.,Fei, F.,Kishor, C.,Leffler, H.,Nilsson, U.J.,Groffen, J.,Grice, I.D.,Heisterkamp, N.,Blanchard, H.
Novel Selective Galectin-3 Antagonists Are Cytotoxic to Acute Lymphoblastic Leukemia.
J.Med.Chem., 65:5975-5989, 2022

PubMed Abstract: Galectin-3 is a β-galactoside-specific, carbohydrate-recognizing protein (lectin) that is strongly implicated in cancer development, metastasis, and drug resistance. Galectin-3 promotes migration and ability to withstand drug treatment of B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cells. Due to high amino acid conservation among galectins and the shallow nature of their glycan-binding site, the design of selective potent antagonists targeting galectin-3 is challenging. Herein, we report the design and synthesis of novel taloside-based antagonists of galectin-3 with enhanced affinity and selectivity. The molecules were optimized by docking, selectivity was established against four galectins, and the binding modes were confirmed by elucidation of X-ray crystal structures. Critically, the specific inhibition of galectin-3-induced BCP-ALL cell agglutination was demonstrated. The compounds decreased the viability of ALL cells even when grown in the presence of protective stromal cells. We conclude that these compounds are promising leads for therapeutics, targeting the tumor-supportive activities of galectin-3 in cancer.

PubMed: 35427125
DOI: 10.1021/acs.jmedchem.1c01296

実験手法

X-RAY DIFFRACTION (1.05 Å)