Liquid Phase Peptide Synthesis via One-Pot Nanostar Sieving (PEPSTAR)
Liquid Phase Peptide Synthesis via One-Pot Nanostar Sieving (PEPSTAR)
复制标题
通过一锅式 Nanostar 筛分法 (PEPSTAR) 进行液相肽合成
DOI：
10.1002/ange.202014445
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发表时间：
2021
影响因子：
--
通讯作者：
Yeo J
中科院分区：
文献类型：
--
作者：
Yeo J
在本文中，报道了一锅液相肽合成，其特征在于将氨基酸反复添加到“nanostar”支持物中，在每个合成循环后用有机溶剂纳滤（OSN）分离生长的肽。一个循环包括偶联、Fmoc去除，然后在反应器-分离器或合成器装置中通过纳滤筛出反应副产物，其中在循环之间不需要相或材料转移。三臂单分散nanostar有助于高效纳滤和每个工艺循环的真实的实时反应监测。这使得能够更有效地合成肽，同时保留液相合成的全部益处。PEPSTAR最初通过合成脑啡肽样模型五肽和十肽，然后是奥曲酯酰胺，最后是奥曲酯进行验证。粗品纯度与供应商从固相合成中生产的样品相比有利。
Herein, a one‐pot liquid phase peptide synthesis featuring iterative addition of amino acids to a “nanostar” support, with organic solvent nanofiltration (OSN) for isolation of the growing peptide after each synthesis cycle is reported. A cycle consists of coupling, Fmoc removal, then sieving out of the reaction by‐products via nanofiltration in a reactor‐separator, or synthesizer apparatus where no phase or material transfers are required between cycles. The three‐armed and monodisperse nanostar facilitates both efficient nanofiltration and real‐time reaction monitoring of each process cycle. This enabled the synthesis of peptides more efficiently while retaining the full benefits of liquid phase synthesis. PEPSTAR was validated initially with the synthesis of enkephalin‐like model penta‐ and decapeptides, then octreotate amide and finally octreotate. The crude purities compared favorably to vendor produced samples from solid phase synthesis.