Strategies for the highly efficient synthesis of erythropoietin N‐glycopeptide hydrazides

Strategies for the highly efficient synthesis of erythropoietin N‐glycopeptide hydrazides
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促红细胞生成素Nâ糖肽酰肼的高效合成策略

DOI:
10.1002/psc.3283
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发表时间:
2020
影响因子:
2.1
通讯作者:
C. Unverzagt
C. Unverzagt
中科院分区:
生物学4区
文献类型:
--
作者:
M. Hessefort;H. Hessefort;S. Seeleithner;A. Gross;M. Lott;D. Rau;L. Kern;C. Unverzagt

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开发了红细胞生成素(EPO)1 - 28 N-糖肽酰肼的会聚合成。在这种方法中,EPO 1 - 28肽在固相上合成,并在从树脂裂解后转化为C-末端酰肼。在Asp 24侧链的选择性脱保护后,通过假脯氨酸辅助的Lansbury双酰化偶联所需的葡糖胺。虽然EPO 1 - 28糖肽的初始产率令人满意,但可以通过使用反相高效液相色谱法(RP-HPLC)纯化受保护的肽来增加肽的纯度来显著提高它们。
A convergent synthesis for erythropoietin (EPO) 1‐28 N‐glycopeptide hydrazides was developed. In this approach, EPO 1‐28 peptides were synthesized on the solid phase and converted to C‐terminal hydrazides after cleavage from the resin. After selective deprotection of the Asp24 side chain, the desired glycosylamine was coupled by pseudoproline‐assisted Lansbury aspartylation. Although the initial yields of the EPO 1‐28 glycopeptides were satisfactory, they could be markedly improved by increasing the purity of the peptide using a reversed‐phase high‐performance liquid chromatography (RP‐HPLC) purification of the protected peptide.
DOI: 10.1002/anie.201205038
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