Cheng Xueheng, Yan Bing, Gao Lan, Tang Hua, Fan Yihong, Anderson Steven N, Affleck Rhett, Burns David J
Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA.
J Biomol Screen. 2005 Jun;10(4):293-303. doi: 10.1177/1087057104272498.
In microarrayed compound screening (microARCS), compounds are spotted and dried onto a polystyrene sheet (ChemCard)ata high density and introduced into the assay by contacting with agarose gels that contain reagents for the assay. The authors have conducted studies to characterize the compound transfer process using 59 compounds of diverse properties. The amount of compounds remaining on the ChemCard was determined by liquid chromatography/mass spectrometry after incubation with agarose gels for predetermined time periods. The results showed good correlation with kinetics of compound transfer to phosphate-buffered saline (PBS) buffer, but only moderate correlation with equilibrium solubility of compounds in PBS buffer. These observations indicate that the major factor determining compound transfer efficiency is the kinetics of dissolution of compounds, rather than equilibrium solubility and diffusion of compounds in the gel. Compounds of lower ClogP showed a higher rate of transfer to agarose gels and vice versa. Other compound properties such as molecular weight, size, acid-base, and H-bonding properties did not significantly affect compound transfer. Importantly, the majority of the compounds studied show greater than 20% transfer after a 10-min incubation with agarose gels, providing sufficient amounts of compounds for screening purposes.
在微阵列化合物筛选（microARCS）中，化合物以高密度点样并干燥在聚苯乙烯片（化学卡片）上，通过与含有检测试剂的琼脂糖凝胶接触引入检测中。作者使用59种性质各异的化合物进行了研究，以表征化合物转移过程。在与琼脂糖凝胶孵育预定时间段后，通过液相色谱/质谱法测定化学卡片上剩余的化合物量。结果表明，与化合物转移到磷酸盐缓冲盐水（PBS）缓冲液的动力学具有良好的相关性，但与化合物在PBS缓冲液中的平衡溶解度仅具有中等相关性。这些观察结果表明，决定化合物转移效率的主要因素是化合物的溶解动力学，而不是化合物在凝胶中的平衡溶解度和扩散。较低ClogP值的化合物向琼脂糖凝胶的转移速率较高，反之亦然。其他化合物性质，如分子量、大小、酸碱性质和氢键性质，对化合物转移没有显著影响。重要的是，大多数研究的化合物在与琼脂糖凝胶孵育10分钟后显示出超过20%的转移率，为筛选目的提供了足够量的化合物。
