对于人类亚亚糖蛋白受体的糖相性联体
Sreeman K Mamidyala1, Sanjay Dutta, Boris A Chrunyk
1Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Journal of the American Chemical Society
|January 28, 2012
概括
研究人员开发了新的galactosyl类似物,可显著增强与亚亚糖蛋白受体 (ASGPR) 的结合亲和力. 这些改进的配体对治疗剂的向性肝脏输送具有前景.
科学领域:
- 生物化学 生物化学
- 药物运输 药物运输 药物运输
- 肝病学 肝病学是一种肝病学.
背景情况:
- 亚亚糖蛋白受体 (ASGPR) 是一个肝细胞表达的受体,对含有银河糖的连接键至关重要.
- 原生ASGPR基质具有较低的结合亲和力,因此需要更强大的配体来有效地输送肝脏.
研究的目的:
- 合成和评估具有对ASGPR增强 afinity的新型 galactosyl 类似物.
- 为了探索 galactosyl 部分的各种位置的修改,以改进连接体设计.
主要方法:
- 合成多种类型的galactosyl类似物,在异构,C2,C5和C6位置进行替代.
- 对ASGPR合成类型的结合亲和力的评估.
主要成果:
- 几种trifluoromethylacetamide衍生物显示出显著增加的结合亲和力.
- 新的配体获得了与N-乙甲胺相似或超过的亲和力.
- 在C3,C4-二醇的两侧的修改被很好地容忍,与浅粘结口袋模型保持一致.
结论:
- 银河系酸盐基因因型适合功能化,用于增强ASGPR向.
- 开发的配体具有低微分子或更高的亲和力,适合治疗有效载荷的附着.
- 这些发现为先进的肝药物输送系统铺平了道路.
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