The aspartimide problem in Fmoc-based SPPS. Part III
The aspartimide problem in Fmoc-based SPPS. Part III
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DOI：
10.1002/psc.668
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发表时间：
2005-10-01
影响因子：
2.1
通讯作者：
Dick, F
中科院分区：
文献类型：
--
作者：
Mergler, M;Dick, F
一种新开发的Fmoc-Asp衍生物，Fmoc-Asp β-（2，3，4-三甲基-天冬-3-基）酯，已在H-Val-Lys-Asp-Xaa-Tyr-Ile-OH的基于Fmoc的SPPS中进行了尝试，该SPPS是用于研究碱催化天冬酰胺形成的良好肽模型。当合成包含Gly、Arg（Pbf）、Asn（Mtt）、Asp（OtBu）或Cys（Acm）的Xaa六肽时，预期会产生大量天冬酰胺相关副产物。Asp（3）β-羧基保护基和暴露于碱的持续时间是不同的。通过引入新的Asp衍生物可以比引入体积较小的Asp（OMpe）更有效地减少副产物的形成。在长期接触哌啶或DBU的情况下观察到显著改善。两个β-羧基保护基都上级本研究中也包括的标准Asp（OtBu），但我们的新保护基获得的额外稳定性非常有价值，特别是在长肽或困难序列的合成中。版权所有（c）2005欧洲肽协会和约翰威利父子有限公司。
A newly developed Fmoc-Asp derivative, Fmoc-Asp beta-(2,3,4-trimethyl-pent-3-yl) ester, has been tried in the Fmoc-based SPPS of H-Val-Lys-Asp-Xaa-Tyr-Ile-OH, a well-established peptide model for studying base-catalysed aspartimide formation. When synthesizing the hexapeptide incorporating Gly, Arg(Pbf), Asn(Mtt), Asp(OtBu) or Cys(Acm) for Xaa, considerable amounts of aspartimide-related by-products were to be expected. The Asp(3) beta-carboxy protecting group and the duration of exposure to bases were varied. By-product formation could be reduced by incorporation of the new Asp derivative more efficiently than by introducing the less bulky Asp(OMpe). Significant improvements were observed in cases of prolonged contact with piperidine or DBU. Both beta-carboxy protecting groups were superior to the standard Asp(OtBu) which was also included in this study, but the additional stabilization gained by our new protecting group was valuable especially in syntheses of long peptides or difficult sequences. Copyright (c) 2005 European Peptide Society and John Wiley & Sons, Ltd.