阳离子选择性胆固醇装饰的宏环转膜离子载体
Harekrushna Behera1, Nandita Madhavan1,2
1Department of Chemistry, Indian Institute of Technology , Madras, Tamil Nadu 600036, India.
Journal of the American Chemical Society
|September 7, 2017
概括
研究人员开发了新型的三化物宏循环,作为合成离子转运器. 这些胆固醇附着的宏循环对化物和酸具有很高的选择性,为离子运输障碍提供了潜在的治疗应用.
科学领域:
- 生物化学
- 医学化学
- 分子生物学
背景情况:
- 阴离子转运器对细胞功能至关重要, 它们的功能障碍与囊性纤维化,和巴特综合征等疾病有关.
- 合成化物转运剂已经证明能够在癌细胞系中诱导亡,这表明其具有治疗潜力.
研究的目的:
- 合成和描述新型的三化物宏循环作为潜在的离子载体.
- 评估合成的宏循环的离子运输活性,选择性和机制.
- 探索这些宏循环在调节离子运输中的治疗潜力.
主要方法:
- 有各种悬挂功能组的三胺宏循环的合成.
- 使用EC50值对阳离子运输活动的评估,确定胆固醇为最佳附加组.
- 确定离子选择性和阐明传输机制 (OH-/X-反端口).
主要成果:
- 成功合成了易于功能化的三化物宏循环.
- 胆固醇附着的宏循环具有强烈的活性,EC50为0. 44μM.
- 宏循环显示出高离子选择性,更喜欢SCN和Cl,并通过OH-/X-反端口机制运行.
结论:
- 三胺宏循环是开发高离子选择性传送器的有希望的支架.
- 这些合成载体可以有效地区分各种离子,首选SCN-和Cl-.
- 开发的宏循环作为研究离子运输的有价值的模型系统,并具有与离子运输失调相关的疾病治疗应用的潜力.
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