脂蛋白合成新进展

生物体内的信号传导蛋白在膜上的定位与其生物功能的发挥依赖于特定脂肪链的修饰,然而传统的基因表达法合成脂蛋白,得到的纯品产率很低.在近10年中,逐渐发展起来一种新的合成方法,即将化学合成脂修饰的多肽与基因表达培养蛋白相结合,可以合成出具有多条脂肪链修饰的蛋白缀合物,并且整个合成过程在非常温和的环境中进行,产品能保持较高的纯度和活性.采用该方法合成的脂蛋白用于体外的实验中,其结果与生物体内的现象非常接近.脂蛋白合成方法的发展对研究细胞中的信号传导过程具有重要的意义,并在药物合成和提高药效方面都有很多应用,这对于研究恶性肿瘤等疾病的发病机理起到了重要的推动作用.同时该脂蛋白合成的成功是采用化学法合成生物大分子解释生物体内的现象一个重大的突破,是化学生物学发展重要的一步.

Progresses in Synthesis of Lipoproteins

Membrane localization and function of many signal proteins in higher eukaryotes are dependent on their covalent modification by specific lipids. However, because of the acid- and base-lability of lipoproteins, the synthesis of protein conjugates is severely complicated. In this paper, we review novel strategies to synthesize lipid-modified proteins, involving the bacterial expression of a carboxy-terminal truncated non-lipidated proteins and the chemical synthesis of differently lipidated peptides representing the C-terminus of the proteins and their covalent coupling. As representative lipoproteins, Ras-derived peptides and fully functional Ras proteins containing different lipid modification can efficiently be synthesized by the bioorganic method that combines the use of enzymatic protecting group with the technique of noble-metal catalyzed removal of blocking functions. These compounds used in cell biological experiment exhibit properties which are very similar to fully processed Ras open for selective modifications, which can be produced in high yields. The development of methods for the synthesis of lipoproteins will benefit the research of signal transduction and oncogenic variants in organism. The chemical synthesis and biological application of lipoproteins have crossed the barrier and bridge the undoubted gap in research culture between chemistry and biology, leading to new stimuli for chemical-biological research.