We previously developed a conjugate consisting of ¹⁰B cluster BSH and tri-arginine peptide (BSH-3R). This could potentially be used as a boron agent for boron neutron capture therapy; however, it possesses poor water solubility and thus needs to be improved for use as medicine. In this study, we devised several means of improving the water solubility of BSH-3R. As one of them, we used cyclodextrin (CD), which was expected to improve the water solubility resulting from interaction of the BSH-3R with CD. We evaluated the solubility of BSH-3R in aqueous CD solution by using reverse-phase high-performance liquid chromatography. As we expected, the solubility of BSH-3R was increased in a manner dependent on the addition of β-CD and γ-CD in aqueous solution. Furthermore, we synthesized BSH conjugated to oligoarginine having various chain lengths (BSH-nR) and BSH-3R with ethylene glycol linkers introduced between BSH and 3R (BSH-nEg-3R). The water solubility of these BSH peptides was also evaluated and the results showed that the introduction of nEg to BSH-3R markedly improved the water solubility. Furthermore, we found that the water solubility of these peptides can be further improved by also applying CD.

中文翻译：

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通过与乙二醇连接基偶联以及与环糊精相互作用提高巯基十二氢十硼酸巯基硼酸乙酯（BSH）肽的水溶性

我们之前开发了由^10个组成的共轭物B簇BSH和三精氨酸肽（BSH-3R）。这有可能被用作硼中子俘获疗法的硼剂。但是，其水溶性差，因此需要改进以用作药物。在这项研究中，我们设计了几种改善BSH-3R水溶性的方法。作为其中之一，我们使用了环糊精（CD），它有望改善BSH-3R与CD相互作用而产生的水溶性。我们通过使用反相高效液相色谱法评估了BSH-3R在CD水溶液中的溶解度。正如我们所期望的，BSH-3R的溶解度以依赖于水溶液中β-CD和γ-CD添加的方式增加。此外，我们合成了具有不同链长（BSH-nR）和BSH-3R的低聚精氨酸的BSH，并在BSH和3R（BSH-nEg-3R）之间引入了乙二醇连接基。还评估了这些BSH肽的水溶性，结果表明将nEg引入BSH-3R显着改善了水溶性。此外，我们发现这些肽的水溶性也可以通过应用CD来进一步改善。