A Synthetic Receptor for Asymmetric Dimethyl Arginine
A Synthetic Receptor for Asymmetric Dimethyl Arginine
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DOI：
10.1021/ja307907p
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发表时间：
2013-05-01
影响因子：
15
通讯作者：
Waters, Marcey L.
中科院分区：
文献类型：
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作者：
James, Lindsey I.;Beaver, Joshua E.;Waters, Marcey L.
利用动态组合化学技术鉴定了一种新的小分子受体A（2）D，它是不对称二甲基精氨酸（aRMe（2））的受体，是蛋白质的翻译后修饰（PTM）。已知它在许多疾病中发挥作用，包括脊髓性肌萎缩症、白血病、淋巴瘤和乳腺癌。该受体表现出2.5-7.5倍的选择性超过异构体对称的二甲基精氨酸，这取决于周围的序列，在低微摩尔范围内的结合亲和力。A（2）D对Arg不同甲基化状态的亲和力和选择性与结合这些PTM的蛋白质的亲和力和选择性相似。受体-PTM复合物的表征表明阳离子-π相互作用提供了结合的主要驱动力，松散地模拟了天然蛋白质受体识别二甲基精氨酸中发现的结合模式。
Dynamic combinatorial chemistry was utilized to identify a novel small molecule receptor, A(2)D, for asymmetric dimethyl arginine (aRMe(2)), which is a post-translational modification (PTM) in proteins. It is known to play a role in a number of diseases, including spinal muscular atrophy, leukemia, lymphoma, and breast cancer. The receptor exhibits 2.5-7.5-fold selectivity over the isomeric symmetric dimethyl arginine, depending on the surrounding sequence, with binding affinities in the low micromolar range. The affinity and selectivity of A(2)D for the different methylated states of Arg parallels that of proteins that bind to these PTMs. Characterization of the receptor-PTM complex indicates that cation-pi interactions provide the main driving force for binding, loosely mimicking the binding mode found in the recognition of dimethyl arginine by native protein receptors.