完全合成的颗粒细胞殖民地刺激因子,通过大,侧链无保护的异介导合来实现
Andrew G Roberts, Eric V Johnston, Jae-Hung Shieh
1Department of Chemistry, Columbia University , New York, New York 10027, United States.
Journal of the American Chemical Society
|September 25, 2015
概括
这项研究提出了一个新的合成平台,用于制造人体颗粒细胞殖民地刺激因子 (G-CSF) 糖. 这种方法允许G-CSF与同质糖形式的选择性合成,有助于糖化研究
科学领域:
- 生物化学
- 葡萄糖生物学
- 合成化学
背景情况:
- 人类颗粒细胞殖民地刺激因子 (G-CSF) 是一个对血液形成至关重要的糖蛋白.
- 临床G-CSF变种 (列诺格拉斯蒂姆,菲尔格拉斯蒂姆) 治疗中性质衰竭,但Thr133的O- 结合糖化作用仍有争议.
- 需要用于功能研究的合成同质G-CSF糖形式的方法.
研究的目的:
- 开发一个合成平台来生产G-CSF糖.
- 为了使本地和设计的G-CSF糖形具有糖素同质性的选择性合成.
- 调查G-CSF糖化中的功能作用.
主要方法:
- 开发一种以异酸为媒介的合成方法.
- C端基酸与未受保护的N端的化学选择性合.
- G-CSF的整体合成.
主要成果:
- 成功开发了一种新型的G-CSF糖合成平台.
- 证明一种高效的以异为媒介的结合,用于合成易于聚合的大型.
- 建立了一种生产同质G-CSF糖形式的方法.
结论:
- 合成平台提供了G-CSF甘氨酸和同质甘氨酸形式.
- 在复杂的合成中,以异酸为媒介的结合是有效的.
- 这项工作有助于进一步研究G-CSF的糖化和功能.
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