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A Potent Mimetic of the Siglec‐8 Ligand 6’‐Sulfo‐Sialyl Lewisx
ChemMedChem ( IF 3.4 ) Pub Date : 2020-09-04 , DOI: 10.1002/cmdc.202000649
Blijke S. Kroezen 1 , Gabriele Conti 1 , Benedetta Girardi 1 , Jonathan Cramer 1 , Xiaohua Jiang 1 , Said Rabbani 1 , Jennifer Müller 1 , Maja Kokot 1 , Enrico Luisoni 1 , Daniel Ricklin 1 , Oliver Schwardt 1 , Beat Ernst 1
Affiliation  

The Front Cover shows the interaction of the natural ligand 6′‐sulfo‐sialyl Lewisx and a glycomimetic thereof with Siglec‐8, a cell‐surface receptor considered to be a promising target for the treatment of eosinophil‐ and mast‐cell‐associated diseases such as asthma. Using a combination of pharmacophore analysis, NMR structural information, and chemical modification of the initial hit identified by glycan array screening, Ernst and co‐workers were able to generate a high‐affinity glycomimetic. The elucidation of the structure—activity relationship, accompanied by the analysis of binding thermodynamics and kinetics, sheds light on the underlying binding mechanisms. These results exhibit an important contribution to the further development of the therapeutic potential of Siglec‐8 antagonists. (Cover graphics by Gabriele Conti, Department of Pharmaceutical Sciences, University of Basel.) More information can be found in the Full Paper by Beat Ernst et al.
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中文翻译:

Siglec-8配体6'-磺基唾液酸Lewisx的强效模拟物

封面显示了天然配体6'-磺基唾液酸Lewis x的相互作用以及它的糖模拟药Siglec-8,一种细胞表面受体,被认为是治疗嗜酸性粒细胞和肥大细胞相关疾病(例如哮喘)的有希望的靶标。结合使用药效基团分析,NMR结构信息和通过聚糖阵列筛选确定的初始命中的化学修饰,Ernst和他的同事能够产生高亲和力的糖模拟物。对结构-活性关系的阐明,以及对结合热力学和动力学的分析,揭示了潜在的结合机理。这些结果显示出对Siglec-8拮抗剂治疗潜力的进一步发展的重要贡献。(巴塞尔大学药物科学系Gabriele Conti的封面图片。
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更新日期:2020-09-14
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