下一代发针聚胺与 (R) -3,4-二氨基黄油酸转换单元
Christian Dose1, Michelle E Farkas, David M Chenoweth
1Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA.
Journal of the American Chemical Society
|May 8, 2008
概括
研究人员使用β-amino-gamma-turn单位开发了新的pyrrole-imidazole发针聚胺. 这些分子表现出增强的DNA结合,并可以抑制基因表达,表明治疗应用的潜力.
科学领域:
- 化学生物学 化学生物学
- 分子生物学分子生物学
- 药物发现 药物发现 药物发现
背景情况:
- role-imidazole聚胺因其结合DNA小沟的能力而闻名.
- 标准聚胺通常使用α-amino-gamma-turn单元进行DNA识别.
研究的目的:
- 为了合成和表征一种新的类型的头聚胺,其中包括β-氨基--转单元.
- 评估这些新型聚胺对DNA双重稳定和结合亲和力的影响.
- 评估这些聚胺在抑制基因表达中的生物活性.
主要方法:
- 一个包含 (R) - 和 (S) -3,4-二氨基黄油酸 (β-氨基--转) 的八种头聚胺库的合成.
- 化温度分析以研究DNA双重稳定性并比较结合亲和力.
- 在细胞培养中评估抑制雄激素受体介导基因表达的生物学测试.
主要成果:
- 与某些序列组合中的α-amino-gamma-turn相比,β-amino-gamma-turn的两种酶体形式都增加了DNA结合亲和力.
- (R) - β - 氨基酸 - 马转向聚胺证明了细胞透性,并抑制了受受体介导的基因表达.
- 新型β-氨基--转聚胺的生物活性与标准聚胺相比较.
结论:
- β-氨基--转单元是构建有效毛聚胺合物的可行的替代方案.
- 这些新型聚胺表现出有希望的DNA结合特性和潜在治疗开发的生物活性.
- 这些发现表明, (R) - β - 氨基 - 玛 - 转聚胺是细胞透的,可以调节基因表达.
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