A gulose moiety contributes to the belomycin (BLM) disaccharide selective targeting to lung cancer cells
A gulose moiety contributes to the belomycin (BLM) disaccharide selective targeting to lung cancer cells
复制标题
古洛糖部分有助于贝霉素 (BLM) 二糖选择性靶向肺癌细胞
DOI：
10.1016/j.ejmech.2021.113866
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发表时间：
2021
影响因子：
6.7
通讯作者：
Zhou Wen
中科院分区：
文献类型：
--
作者：
Zhou Cui;Ye Wenchong;Cao Yongjun;Wang Meizhu;Qi Dongxia;Liao Guohao;Li Houkai;Huang Weiping;Chen Wenming;Wang Xiaoyang;Zhou Wen
本研究设计并合成了8个BLM二糖衍生的单糖或二糖类似物，沿着合成了相应的糖-染料缀合物，旨在探讨古洛糖残基对BLM二糖细胞结合/摄取的影响及其可能的摄取机制。我们的证据表明，对于BLM二糖的细胞结合/摄取，古洛糖残基是一个重要的亚基，但与其化学性质无关。有趣的是，d-古洛糖-染料缀合物能够选择性地靶向A549癌细胞，但l-古洛糖-染料缀合物失败。进一步的摄取机制研究表明，古洛糖染料衍生物类似于BLM dislidide染料的行为在温度和ATP依赖性的方式，部分是由GLUT 1受体。此外，d-古洛糖修饰的吉西他滨53 a与吉西他滨用其他单糖修饰的衍生物53 b-cin相比表现出更强的抗肿瘤活性。总之，单糖-古洛糖缀合物通过增加肺癌治疗中的肿瘤靶向为解决细胞毒性药物提供了新的策略。
Eight mono- or disaccharide analogues derived from BLM disaccharide, along with the corresponding carbohydate-dye conjugates have been designed and synthesized in this study, aiming at exploring the effect of a gulose residue on the cellular binding/uptake of BLM disaccharide and it possible uptake mechanism. Our evidence is presented indicating that, for the cellular binding/uptake of BLM disaccharide, a gulose residue is an essential subunit but unrelated to its chemical nature. Interestingly,d-gulose-dye conjugate is able to selectively target A549 cancer cells, butl-gulose-dye conjugate fails. Further uptake mechanism studies demonstrated-gulose-dye derivatives similar to BLM disaccharide-dye ones behave in a temperature- and ATP-dependent manner, and are partly directed by the GLUT1 receptor. Moreover,d-gulose modifying gemcitabine53aexhibits more potent antitumor activity compared to derivatives53b-cin which gemcitabine is decorated with other monosaccharides. Taken together, the monosacharided-gulose conjugate offers a new strategy for solving cytotoxic drugs via the increased tumor targeting in the therapy of lung cancer.