The depsipeptide technique applied to peptide segment condensation: Scope and limitations
The depsipeptide technique applied to peptide segment condensation: Scope and limitations
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缩酚肽技术应用于肽片段缩合：范围和局限性
DOI：
10.1002/psc.928
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发表时间：
2008
影响因子：
2.1
通讯作者：
M. Beyermann
中科院分区：
文献类型：
--
作者：
Irene Coin;P. Schmieder;M. Bienert;M. Beyermann
最近提出了缩肽技术的一个有前景的应用，为片段缩合提供理想的条件，因为带有C末端缩肽单元的肽的偶联发生而不会在活化的氨基酸处引起差向异构化。这是由于与相应的肽段相比，活化的缩肽单元形成光学不稳定的恶唑酮的倾向较低。在这项工作中，我们证明了使用HBTU通过碱辅助活化进行的缩肽偶联不仅不会损失构型，而且比相应的所有酰胺片段的偶联快得多。然而，当长缩肽片段的偶联缓慢进行时，我们发现在活化的缩肽单元处发生β消除，其程度取决于系统中碱的存在和溶剂的类型。通过在非极性溶剂（DCM）中使用碳二亚胺/HOBt活化完全抑制β-消除，并且在更极性的介质中，通过在HBTU活化期间用TMP代替DIEA或使用特定的溶剂混合物（例如DMSO/甲苯）经由碳二亚胺活化来限制β-消除。最后，我们展示了C-末端假脯氨酸的应用，与缩肽单元的应用进行比较，以进行片段偶联。版权所有© 2007年欧洲肽协会和约翰威利父子有限公司。
A promising application of the depsipeptide technique has recently been proposed to provide ideal conditions for segment condensation, in that coupling of peptides bearing a C‐terminal depsipeptide unit occurs without giving rise to epimerization at the activated amino acid. This is due to the low tendency of the activated depsipeptide units, in contrast to the corresponding peptide segments, to form optically labile oxazolones. In this work we demonstrate that coupling of depsipeptides via base‐assisted activation using HBTU occurs not only without loss of configuration, but even much faster than the coupling of the corresponding all‐amide segments. Nevertheless, when the coupling of long depsipeptide segments proceeds slowly, we uncovered the occurrence of β‐elimination at the activated depsipeptide unit, in an extent dependent on the presence of base in the system and on the type of the solvent. Beta‐elimination was completely suppressed by using carbodiimide/HOBt activation in a non‐polar solvent (DCM), and in more polar media it was limited by substituting TMP for DIEA during HBTU activation, or using particular solvent mixtures (such as DMSO/toluene) for activation via carbodiimide. Finally, we show the application of C‐terminal pseudoprolines, in comparison with that of depsipeptide units, to segment coupling. Copyright © 2007 European Peptide Society and John Wiley & Sons, Ltd.
DOI：
--
发表时间：
1994
期刊：
American biotechnology laboratory
影响因子：
--
作者：
Rabinovich,AK;Rivier,JE
通讯作者：
Rivier,JE