Total synthesis of the α-subunit of human glycoprotein hormones: toward fully synthetic homogeneous human follicle-stimulating hormone.

Total synthesis of the α-subunit of human glycoprotein hormones: toward fully synthetic homogeneous human follicle-stimulating hormone.
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DOI:
10.1021/ja2111459
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发表时间:
2012-02-22
影响因子:
15
通讯作者:
Danishefsky, Samuel J.
Danishefsky, Samuel J.
中科院分区:
化学1区
文献类型:
--
作者:
Aussedat, Baptiste;Fasching, Bernhard;Johnston, Eric;Sane, Neeraj;Nagorny, Pavel;Danishefsky, Samuel J.

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本文描述了首次全化学合成独特的人糖蛋白激素α亚基(α-hGPH)。与生物来源的糖蛋白激素以高度复杂的糖形式混合物的形式分离不同,通过化学合成获得的α-hGPH含有离散的均一糖形式。已经准备了两个这样的系统。一种是天然N-糖基化位点上的二糖壳二糖。另一个在这些相同的位置含有十二聚体低聚糖。十二聚体糖是一个包含与人类糖蛋白相关的关键特征的共识序列。
Described herein is the first total chemical synthesis of the unique α-subunit of the human glycoprotein hormone (α-hGPH). Unlike the biologically–derived glycoprotein hormones, which are isolated as highly complex mixtures of glycoforms, α-hGPH obtained by chemical synthesis contains discrete homogeneous glycoforms. Two such systems have been prepared. One contains the disaccharide chitobiose at the natural N-glycosylation sites. The other contains dodecamer oligosaccharides at these same sites. The dodecamer sugar is a consensus sequence incorporating the key features associated with human glycoproteins.
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