The diisopropylcarbodiimide/1-hydroxy-7-azabenzotriazole system: Segment coupling and stepwise peptide assembly
The diisopropylcarbodiimide/1-hydroxy-7-azabenzotriazole system: Segment coupling and stepwise peptide assembly
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DOI：
10.1016/s0040-4020(99)00344-0
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发表时间：
1999-05-28
期刊：
影响因子：
2.1
通讯作者：
El-Faham, A
中科院分区：
文献类型：
--
作者：
Carpino, LA;El-Faham, A
对于一组模型肽段，通过溶液或固相技术进行的偶联反应已经证明了DIC/HOAt系统优于DIC/HOBt系统，此外，对于涉及其他选择的双酰亚胺和取代的HOBt衍生物的系统，具有吸电子取代基。无论使用何种添加剂，在DCM中发生的构型损失（如果有的话）非常少，尽管在溶剂如DMF中效率的相对顺序是相似的，其中产生更广泛的差向异构化。在DIC/HOAt通过固相技术逐步肽组装的应用中，发现受阻吡啶碱可力丁增强了涉及羧酸残基的预活化的步骤，与其中碱如DIEA、NMM或非受阻吡啶碱抑制该步骤的正常情况相反。这些结果导致开发了用于肽组装的逐步程序，其中加入可力丁以增强活化，随后加入DIEA以增强偶联，（C）1999 Elsevier Science Ltd.保留所有权利。
For a group of model peptide segments, coupling reactions carried out via solution or solid phase techniques have demonstrated the advantages of the system DIC/HOAt over DIC/HOBt and in addition for systems involving other selected carbodiimides and substituted HOBt derivatives bearing electron-withdrawing substituents. Very little, if any, loss of configuration occurred in DCM regardless of the additive used, although the relative order of efficiency was similar in solvents such as DMF in which more extensive epimerization resulted. In application of DIC/HOAt to stepwise peptide assembly by solid phase techniques, it was found that the hindered pyridine base collidine enhanced the step involving preactivation of the carboxylic acid residue in contrast to the normal situation in which bases such as DIEA, NMM, or non-hindered pyridine bases inhibit this step. These results led to development of a stepwise procedure for peptide assembly in which collidine is added to enhance activation and subsequently DIEA is added to enhance coupling, (C) 1999 Elsevier Science Ltd. All rights reserved.