Chemical Synthesis of O-Glycosylated Human Interleukin-2 by the Reverse Polarity Protection Strategy
Chemical Synthesis of O-Glycosylated Human Interleukin-2 by the Reverse Polarity Protection Strategy
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DOI：
10.1002/anie.201501847
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发表时间：
2015-07-06
影响因子：
16.6
通讯作者：
Hojo, Hironobu
中科院分区：
文献类型：
--
作者：
Asahina, Yuya;Komiya, Shinobu;Hojo, Hironobu
本文报道了用连接法化学合成人白细胞介素-2（IL-2）。虽然IL-2是一种球状糖蛋白，但其C-末端区域，特别是（99-133），在通过固相法合成时是极不溶的。为了克服这个问题，Glu残基的侧链羧酸被吡啶甲酸酯保护，从而将其极性从负极性反转为正极性。这种反极性保护显著提高了肽段的等电点，使其在酸性条件下呈阳性，有利于纯化。还开发了一种有效的方法来制备（28-65）片段合成所需的脯氨酰肽硫酯。这些努力导致具有完全生物活性的糖基化IL-2的全合成。
The chemical synthesis of human interleukin-2 (IL-2), having a core 1 sugar, by a ligation method is reported. Although IL-2 is a globular glycoprotein, its C-terminal region, in particular (99-133), is extremely insoluble when synthesized by solid-phase method. To overcome this problem, the side-chain carboxylic acid of the Glu residues was protected by a picolyl ester, thus reversing its polarity from negative to positive. This reverse polarity protection significantly increased the isoelectric point of the peptide segment and made it positive under acidic conditions and facilitated the purification. An efficient method to prepare the prolyl peptide thioester required for the synthesis of the (28-65) segment was also developed. These efforts resulted in the total synthesis of the glycosylated IL-2 having full biological activity.