Depsipeptide methodology for solid-phase peptide synthesis:: Circumventing side reactions and development of an automated technique via depsidipeptide units
Depsipeptide methodology for solid-phase peptide synthesis:: Circumventing side reactions and development of an automated technique via depsidipeptide units
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DOI：
10.1021/jo060914p
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发表时间：
2006-08-04
影响因子：
3.6
通讯作者：
Carpino, Louis A.
中科院分区：
文献类型：
--
作者：
Coin, Irene;Doelling, Rudolf;Carpino, Louis A.
缩肽技术是最近开发的用于肽合成的方法，当由于聚集现象而出现合成困难时，其适用于困难序列。在目前的工作中，应用缩肽的方法，以极其困难的序列已被证明和一个严重的副反应，涉及二酮哌嗪形成发现，并随后避免适当使用的Bsmoc保护基团。已经研究了该技术的许多其他方面，例如在组装和后处理过程中depsi单元的稳定性、O-酰化步骤的完整性、O-酰化过程中活化的氨基酸的差向异构化的发生以及形成的副产物的性质。此外，该方法进行了修改，以允许完全自动化的合成长链缩肽，而不需要任何中断手动酯化程序。最后，新的缩肽技术的合成效率被证明是可比的，众所周知的假脯氨酸技术。
The depsipeptide technique is a recently developed method for peptide synthesis which is applicable to difficult sequences when the synthetic difficulty arises because of aggregation phenomena. In the present work, application of the depsipeptide method to extremely difficult sequences has been demonstrated and a serious side reaction involving diketopiperazine formation uncovered and subsequently avoided by the appropriate use of the Bsmoc protecting group. Many other aspects of the technique have been investigated, such as the stability of the depsi units during assembly and workup procedures, the completeness of the O-acylation step, the occurrence of epimerization of the amino acid activated during O-acylation, and the nature of side products formed. In addition, the method was modified so as to allow for completely automated syntheses of long-chain depsipeptides without the need for any interruption by manual esterification procedures. Finally, the synthesis efficiency of the new depsipeptide technique was shown to be comparable to that of the well-known pseudoproline technique.