C2-symmetrical thiodigalactoside bis-benzamido derivatives as high-affinity inhibitors of galectin-3:: efficient lectin inhibition through double arginine-arene interactions
C2-symmetrical thiodigalactoside bis-benzamido derivatives as high-affinity inhibitors of galectin-3:: efficient lectin inhibition through double arginine-arene interactions
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DOI：
10.1002/anie.200500627
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发表时间：
2005-01-01
影响因子：
16.6
通讯作者：
Nilsson, UJ
中科院分区：
文献类型：
--
作者：
Cumpstey, I;Sundin, A;Nilsson, UJ
胍离子带正电，具有 π 体系，并且在水中的溶剂化性较差，[7] 这使其非常适合与芳香族 π 体系相互作用。因此，靶向具有芳香结构的蛋白质精氨酸残基正在成为蛋白质抑制剂开发的一个有吸引力的策略。硫二半乳糖苷 3 已被证明与半乳糖苷结合，其亲和力与 LacNAc 大致相同，[8]，并且假设它以与 LacNAc 相似的模式结合，[8a]，即在子位点 C 和 D 中，具有相似的构象和氢键网络（图 1b）。这一概念最近在半乳糖凝集素-1 上得到了证实，其 X 射线结构已通过 LacNAc 1 和硫代二半乳糖苷 3 作为配体得到解析。 [8b] 半乳糖残基在两种二糖的 C 子位点中的结合相同，而在 D 子位点中，硫二半乳糖苷的 Gal 和 LacNAc 的 GlcNAc 显示出与蛋白质相同的相互作用模式。
The guanidinium ion is positively charged, has a π system, and is poorly solvated in water,[7] which makes it ideal for interactions with aromatic π systems. Consequently, the targeting of protein arginine residues with aromatic structures is emerging as an attractive strategy for protein inhibitor development.Thiodigalactoside 3 has been shown to bind to galectins with about the same affinity as LacNAc,[8] and it was hypothesized that it bound in a mode similar to that of LacNAc,[8a] that is, in subsitesC and D, with a similar conformation and hydrogen-bonding network (Figure1b). This notion has recently been confirmed for galectin-1, for which X-ray structures have been solved both with LacNAc 1 and with thiodigalactoside 3 as ligands.[8b] The galactose residues bind identically in subsite C for the two disaccharides, and in subsiteD, the Gal of thiodigalactoside and GlcNAc of LacNAc show identical patterns of interaction with the protein.