基于N-乙烯基葡萄糖胺的糖化物有效的酸转移酶抑制剂
Ralf Schwörer1, Richard R Schmidt
1Fachbereich Chemie, Universität Konstanz, Fach M 725, D-78457 Konstanz, Germany.
Journal of the American Chemical Society
|February 21, 2002
概括
研究人员合成了新的N-乙葡萄糖胺衍生物,模仿2,3-脱龙氨酸. 这些化合物有效地抑制α2-6-sialyltransferase,显示作为治疗剂的潜力.
科学领域:
- 药用化学 医学化学
- 葡萄糖化学 葡萄糖化学
- 酶抑制可以抑制酶.
背景情况:
- 阿尔法2-6-基转移酶在细胞过程中起着至关重要的作用.
- 开发这种酶的特定抑制剂对于治疗应用很重要.
研究的目的:
- 为了合成新型过渡状态类型的cytidine单酸-N-乙烯基神经氨基酸.
- 为了评估这些类型的抑制潜力对阿尔法2-6-sialyltransferase.
主要方法:
- 从D-葡萄糖胺开始的化学合成.
- 产生不和阿尔德海德,模仿2,3-脱氨酸.
- 酸盐的添加和CMP残留的附着形成受保护的类似物.
主要成果:
- 合成了受保护的过渡状态类似物 (14a,b) 和它们的非受保护形式 (1ah,l, 1bh,l).
- 通过化合物1ah,l和1bh,l,获得了来自老鼠肝脏的α(2-6) -sialyltransferase的优异抑制.
- 产生的二烯衍生物 (E) - / Z) - 2a,b,也显示出抑制性质.
结论:
- 合成的N-乙葡萄糖胺衍生物是阿尔法2-6-酸转移酶的强有力的抑制剂.
- 这些化合物代表了开发针对基转移酶活性的新治疗策略的有希望的线索.
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