Structure, solubility, and permeability relationships in a diverse middle molecule library
Structure, solubility, and permeability relationships in a diverse middle molecule library
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多种中分子库中的结构、溶解度和渗透性关系
DOI：
10.1016/j.bmcl.2021.127847
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发表时间：
2021
影响因子：
2.7
通讯作者：
Kayoko Kanamitsu et al.
中科院分区：
文献类型：
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作者：
安井猛，巽理寧;山本芳彦;触媒学会（編）;Kayoko Kanamitsu et al.
为了开发预测中分子的潜在可药用性的方法，我们检查了由510个分子（359个天然产物衍生物，76个非天然产物，46个天然产物和29个非天然产物衍生物）组成的多样化库（HKDL版本1）的结构、溶解度和渗透性关系。该文库包括肽、缩肽、大环内酯和木脂素，并且510种化合物中的476种具有500-2000 Da范围内的分子量。采用平行人工膜渗透试验（PAMPA）测定中分子的溶解度和被动扩散速度。获得了471个分子的溶解度和287个分子的被动扩散速度的定量值，并考察了它们与分子结构特征的相关性。在此基础上，我们提出了一种从中分子的三维结构特征预测其被动扩散特性的方法。
To develop methodology to predict the potential druggability of middle molecules, we examined the structure, solubility, and permeability relationships of a diverse library (HKDL ver.1) consisting of 510 molecules (359 natural product derivatives, 76 non-natural products, 46 natural products, and 29 non-natural product derivatives). The library included peptides, depsipeptides, macrolides, and lignans, and 476 of the 510 compounds had a molecular weight in the range of 500–2000 Da. The solubility and passive diffusion velocity of the middle molecules were assessed using the parallel artificial membrane permeability assay (PAMPA). Quantitative values of solubility of 471 molecules and passive diffusion velocity of 287 molecules were obtained, and their correlations with the structural features of the molecules were examined. Based on the results, we propose a method to predict the passive diffusion characteristics of middle molecules from their three-dimensional structural features.