Screening for galectin-3 inhibitors from synthetic lacto-N-biose libraries using microscale affinity chromatography coupled to mass spectrometry
Screening for galectin-3 inhibitors from synthetic lacto-N-biose libraries using microscale affinity chromatography coupled to mass spectrometry
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DOI：
10.1021/jo060485v
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发表时间：
2006-09-15
影响因子：
3.6
通讯作者：
Hindsgaul, Ole
中科院分区：
文献类型：
--
作者：
Fort, Sebastien;Kim, Hyo-Sun;Hindsgaul, Ole
报道了两个β-D-Galp-（1-3）-β-D-GlcpN（乳糖-N-二糖）二糖库的合成和筛选。在HO-2'和NH位置进行液相合成修饰，以增强对半乳糖凝集素-3的亲和力，半乳糖凝集素-3是一种参与肿瘤转移、凋亡和炎症的半乳糖结合蛋白。通过与质谱联用的微型前沿亲和色谱法（FAC/MS）筛选文库的半乳糖凝集素-3结合，从而允许不同抑制剂的快速分级和半乳糖凝集素-3结合K-d的测定。在NH基团上具有疏水取代基的化合物对凝集素表现出最高的亲和力。与N-乙酰基母体化合物（Kd = 73.3 μ M）相比，N-萘甲酰基衍生物（Kd = 10.6 μ M）是亲和力增加7倍的最佳抑制剂。
The synthesis and screening of two beta-D-Galp-(1-3)-beta-D-GlcpN ( lacto-N-biose) disaccharide libraries are reported. Solution-phase synthetic modifications at the HO-2' and NH positions were performed in an effort to enhance the affinity toward galectin-3, a galactose-binding protein involved in tumor metastasis, apoptosis, and inflammation. The libraries were screened for galectin-3 binding by microscale frontal affinity chromatography coupled to mass spectrometry ( FAC/MS) allowing for rapid ranking of the different inhibitors and the determination of the galectin-3 binding K-d's. Compounds bearing a hydrophobic substituent on the NH group showed the highest affinity for the lectin. The N-naphthoyl derivative ( K-d = 10.6 mu M) was the best inhibitor with a 7 times increased affinity as compared to the N-acetyl parent compound ( K-d = 73.3 mu M).