Matsumoto A, Stephenson-Brown A J, Khan T, Miyazawa T, Cabral H, Kataoka K, Miyahara Y
Institute of Biomaterials and Bioengineering , Tokyo Medical and Dental University , 2-3-10 Kanda-Surugadai, Chiyoda-ku , Tokyo 101-0062 , Japan . Email:
School of Chemical Engineering , University of Birmingham , Edgbaston , Birmingham , B15 2TT , UK.
Chem Sci. 2017 Sep 1;8(9):6165-6170. doi: 10.1039/c7sc01905j. Epub 2017 Jul 5.
Boronic acids are well known for their ability to reversibly interact with the diol groups found in sugars and glycoproteins. However, they are generally indiscriminate in their binding. Herein we describe the discovery of a group of heterocyclic boronic acids demonstrating unusually high affinity and selectivity for sialic acids (SAs or -acetylneuraminic acid), which are sugar residues that are intimately linked with tumor growth and cancer progression. Remarkably, these interactions strengthen under the weakly acidic pH conditions associated with a hypoxic tumoral microenvironment. competitive binding assays uncovered a significantly higher ability of 5-boronopicolinic acid, one of the derivatives identified in this work as a strong SA-binder, to interact with cell surface SA in comparison to a gold-standard structure, 3-propionamidophenylboronic acid, which has proven to be an efficient SA-binder in numerous reports. This structure also proved to be suitable for further chemical conjugation with a well-preserved SA-binding capability. These findings suggest an attractive alternative to other ongoing boronic acid based chemistry techniques aiming to achieve tumor-specific chemotherapies and diagnoses.
硼酸因其能够与糖类和糖蛋白中的二醇基团发生可逆相互作用而广为人知。然而，它们的结合通常缺乏特异性。在此，我们描述了一组杂环硼酸的发现，这些硼酸对唾液酸（SAs或N-乙酰神经氨酸）表现出异常高的亲和力和选择性，唾液酸是与肿瘤生长和癌症进展密切相关的糖残基。值得注意的是，在与缺氧肿瘤微环境相关的弱酸性pH条件下，这些相互作用会增强。竞争性结合试验发现，与金标准结构3-丙酰胺基苯硼酸相比，在这项工作中鉴定为强唾液酸结合剂的衍生物之一5-硼吡啶甲酸与细胞表面唾液酸相互作用的能力显著更高，在众多报道中，3-丙酰胺基苯硼酸已被证明是一种有效的唾液酸结合剂。该结构也被证明适用于进一步的化学偶联，且唾液酸结合能力良好。这些发现为其他旨在实现肿瘤特异性化疗和诊断的正在进行的基于硼酸的化学技术提供了一个有吸引力的替代方案。
