合成,结构和生物合成研究一种来自α-dystroglycan的不同寻常的基酸
Kai-For Mo1, Tao Fang, Stephanie H Stalnaker
1Complex Carbohydrate Research Center, University of Georgia, 315 Riverbend Road, Athens, Georgia 30602, USA.
Journal of the American Chemical Society
|August 5, 2011
概括
研究人员开发了一种合成方法来研究alpha-dystroglycan (α-DG) 的异常糖化. 这项研究阐明了O-甘氨酸加工如何调节α-DG功能并影响相关疾病.
科学领域:
- 生物化学 生物化学
- 葡萄糖生物学 葡萄糖生物学
- 有机化学 有机化学
背景情况:
- 异常的α-dystroglycan (α-DG) 糖化与由于细胞外矩阵相互作用受损的各种疾病有关.
- 了解α-DG糖化酶的精确机制对于阐明疾病的发病机制至关重要.
研究的目的:
- 开发一种合成策略,用于制备来自α-DG的酸化O-曼诺西尔糖.
- 调查影响α-DG.关键甘氨酸在α-DG.上形成的调控因素.
- 探索糖化在α-DG和相关病理的翻译后成熟中的作用.
主要方法:
- 采用Fmoc化学和Sieber胺树脂的自动化固相糖合成.
- 制备受保护的类曼诺化物及其与氨酸衍生物的合.
- 使用NMR光谱学合成的糖和减少的三糖的结构确认.
- 使用POMGnT1进行酶分析以评估糖受体活性.
主要成果:
- 一种新的合成途径产生了不寻常的酸化O-曼诺西尔糖和减少的三糖.
- 核磁共振数据证实了基的结构.
- 发现一个6--O-曼诺残留物是POMGnT1的不良受体,与其非化对应物不同.
- POMGnT1活性取决于接受器位点在糖序列中的位置.
- O-曼诺西尔的修改对骨形状的影响最小,但可能会调节后续的O-GalNAc添加.
结论:
- 合成方法提供了对离散的糖结构的访问,用于研究α-DG糖化.
- 这些发现揭示了对α-DG的O-甘氨酸加工的复杂调节,涉及连续的酶化步骤.
- 了解这些调节机制对于解决与低糖化α-DG相关的病理至关重要.
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