Selective Galectin-8N Ligands: The Design and Synthesis of Phthalazinone-d-Galactals

IF 3.6 4区医学 Q2 CHEMISTRY, MEDICINAL

ChemMedChem Pub Date : 2021-12-15 DOI:10.1002/cmdc.202100575

Sjors van Klaveren, Dr. Anders P. Sundin, Prof. ?iga Jakopin, Prof. Marko Anderluh, Prof. Hakon Leffler, Prof. Ulf J. Nilsson, Prof. Tihomir Toma?i?

引用次数: 0

Abstract

Ligand selectivity among the highly conserved galectins has been an ever-challenging objective. For galectin-8, a protein prevalent in both pathology and tissue distribution, we report phthalazinone-galactals that show excellent selectivity for the galectin-8N-terminal domain. A dissection of structure–activity relationships of the phthalazinone and an extensive molecular dynamics meta-analysis accompany the discovery of the selective galectin-8N ligands presented here. These selective compounds will facilitate the study of galectin-8 biology and may have pharmaceutical relevance in the wide range of galectin-8 associated pathologies.

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选择性半乳糖凝集素- 8n配体:酞嗪酮-d-半乳糖的设计与合成

高度保守的凝集素的配体选择性一直是一个具有挑战性的目标。对于半乳糖凝集素-8，一种在病理和组织分布中普遍存在的蛋白质，我们报道了酞嗪酮-半乳糖对半乳糖凝集素- 8n末端结构域表现出极好的选择性。对酞嗪酮的结构-活性关系的解剖和广泛的分子动力学荟萃分析伴随着选择性半乳糖凝集素- 8n配体的发现。这些选择性化合物将促进半乳糖凝集素-8生物学的研究，并可能在广泛的半乳糖凝集素-8相关病理中具有药学相关性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ChemMedChem 医学-药学

CiteScore

6.70

自引率

2.90%

发文量

280

审稿时长

1 months

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