A Tetra-Orthogonal Strategy for the Efficient Synthesis of Scaffolds Based on Cyclic Peptides.
A Tetra-Orthogonal Strategy for the Efficient Synthesis of Scaffolds Based on Cyclic Peptides.
复制标题
基于环肽的支架高效合成的四正交策略。
DOI：
10.1007/s10989-017-9642-0
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发表时间：
2018
影响因子：
2.5
通讯作者：
Friedman,SimonH
中科院分区：
文献类型：
--
作者：
Jain,Nitin;Friedman,SimonH
我们已经开发了一种简单而稳健的策略来合成一系列环肽支架，用于在广泛的方向上呈现定义的部分。具体地说，我们正在探索喹恶啉作为部分，作为一个潜在的核酸结合基序。该方法需要使用四度正交性，这反过来允许主链的延伸、目标侧链的结合、树脂上的环化以及氨基在裂解时的揭示以增加溶解性。我们表明，相关方法的失败有一系列原因，包括环化失败。经过对单一环肽方法的优化，我们合成了一系列可能的双和三喹恶啉加合物，ESI-MS表明在大多数情况下都产生了所需的全长环状产物。
We have developed a straightforward and robust strategy for synthesizing a family of cyclic peptide scaffolds for the presentation of defined moieties in a wide range of orientations. Specifically we are exploring quinoxaline as the moiety, as a potential nucleic acid binding motif. The method requires the use of four degrees of orthogonality, which in turn allow the extension of the main chain, incorporation of the target side chains, on-resin cyclization, and the revelation of an amino group upon cleavage to increase solubility. We show that related approaches fail for a range of reasons, including the failure of cyclization. Following the optimization of the approach with a single cyclic peptide, we synthesized a family of all possible bis and tris quinoxaline adducts showing by ESI–MS that the desired full length cyclic product is produced in a majority of cases.